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Objectives: Although anxiety exists concerning the perceived risk of transmission of bloodborne viruses after community-acquired needlestick injuries, seroconversion seems to be rare. The objectives of this study were to describe the epidemiology of pediatric community-acquired needlestick injuries and to estimate the risk of seroconversion for HIV, hepatitis B virus, and hepatitis C virus in these events., Methods: The study population included all of the children presenting with community-acquired needlestick injuries to the Montreal Children's Hospital between 1988 and 2006 and to Hôpital Sainte-Justine between 1995 and 2006. Data were collected prospectively at Hôpital Sainte-Justine from 2001 to 2006. All of the other data were reviewed retrospectively by using a standardized case report form., Results: A total of 274 patients were identified over a period of 19 years. Mean age was 7.9 +/- 3.4 years. A total of 176 (64.2%) were boys. Most injuries occurred in streets (29.2%) or parks (24.1%), and 64.6% of children purposely picked up the needle. Only 36 patients (13.1%) noted blood on the device. Among the 230 patients not known to be immune for hepatitis B virus, 189 (82.2%) received hepatitis B immunoglobulin, and 213 (92.6%) received hepatitis B virus vaccine. Prophylactic antiretroviral therapy was offered beginning in 1997. Of the 210 patients who presented thereafter, 82 (39.0%) received chemoprophylaxis, of whom 69 (84.1%) completed a 4-week course of therapy. The use of a protease inhibitor was not associated with a significantly higher risk of adverse effects or early discontinuation of therapy. At 6 months, 189 were tested for HIV, 167 for hepatitis B virus, and 159 for hepatitis C virus. There were no seroconversions., Conclusions: We observed no seroconversions in 274 pediatric community-acquired needlestick injuries, thereby confirming that the risk of transmission of bloodborne viruses in these events is very low.

A clinical trial has shown that a live-attenuated varicella-zoster virus vaccine is effective against herpes zoster (HZ) and post-herpetic neuralgia (PHN). The aim of this study was to examine the cost-effectiveness of vaccination against HZ and PHN in Canada. A cohort model was developed to estimate the burden of HZ and the cost-effectiveness of HZ vaccination, using Canadian population-based data. Different ages at vaccination were examined and probabilistic sensitivity analysis was performed. The economic evaluation was conducted from the ministry of health perspective and 5% discounting was used for costs and benefits. In Canada (population = 30 million), we estimate that each year there are 130,000 new cases of HZ, 17,000 cases of PHN and 20 deaths. Most of the pain and suffering is borne by adults over the age of 60 years and is due to PHN. Vaccinating 65-year-olds (HZ efficacy = 63%, PHN efficacy = 67%, no waning, cost/course = $150) is estimated to cost $33,000 per QALY-gained (90% CrI: 19,000-63,000). Assuming the cost per course of HZ vaccination is $150, probabilistic sensitivity analysis suggest that vaccinating between 65 and 75 years of age will likely yield cost-effectiveness ratios below $40,000 per Quality-Adjusted Life-Year (QALY) gained, while vaccinating adults older than 75 years will yield ratios less than $70,000 per QALY-gained. These results are most sensitive to the duration of vaccine protection and the cost of vaccination. In conclusion, results suggest that vaccinating adults between the ages of 65 and 75 years is likely to be cost-effective and thus to be a judicious use of scarce health care resources.

The fibroblast growth factors (FGFs) exert their diverse (or pleiotropic) biological responses through the binding and activation of specific cell surface receptors (FGFRs). While FGFRs are known to initiate intracellular signaling through receptor tyrosine phosphorylation, the precise mechanisms by which the FGFRs regulate pleiotropic biological responses remain unclear. We now identify a new mechanism by which FGFR2 is able to regulate intracellular signaling and cellular responses. We show that FGFR2 is phosphorylated on serine 779 (S779) in response to FGF2. S779, which lies adjacent to the phospholipase Cgamma binding site at Y766, provides a docking site for the 14-3-3 phosphoserine-binding proteins and is essential for the full activation of the phosphatidylinositol 3-kinase and Ras/mitogen-activated protein kinase pathways. Furthermore, S779 signaling is essential for promoting cell survival and proliferation in both Ba/F3 cells and BALB/c 3T3 fibroblasts. This new mode of FGFR2 phosphoserine signaling via the 14-3-3 proteins may provide an increased repertoire of signaling outputs to allow the regulation of pleiotropic biological responses. In this regard, we have identified conserved putative phosphotyrosine/phosphoserine motifs in the cytoplasmic domains of diverse cell surface receptors, suggesting that they may perform important functional roles beyond the FGFRs.

Unlabelled: Nontuberculous mycobacteria (NTM) infections seem to be increasing in numbers and in severity in developed countries worldwide., Objective: To document the severity and to assess whether an increase in cases has occurred over the years, we described the epidemiology, clinical presentation, investigations, and treatment of NTM adenitis seen at the Montreal Children's Hospital., Methods: Cases were identified through revision of the microbiology laboratory database for positive NTM culture from any site and through retrieval by the medical records of charts of patients with a diagnosis of adenitis and a node biopsy or excision or a diagnostic code of NTM disease, between 1990 and 2004. These charts were reviewed retrospectively., Results: Over the 15-year period, we identified 36 patients with a median age of 2.8 years with NTM adenitis. Of these cases, 22 (61%) occurred in the past 5 years. Only 3 children were born outside Canada. The majority (92%) presented with a cervicofacial mass, and 25% had constitutional symptoms or fever. There were 3 cases of mediastinal adenitis and 2 cases of cervical disease extending to the deep neck vessels, all of which occurred in the past 5 years. The purified protein derivative (PPD) test for tuberculosis was positive (> or = 10 mm) in 11 of 15 patients tested (73%), none of whom had ever had contact with tuberculosis. Thirty-three patients had surgery. Of the 26 patients who had excisional biopsy or functional neck dissection, 15% required a second surgery for persistence or recurrence compared with 100% of those who had incision and drainage or curettage. Cultures were positive in 72% of the 32 specimens sent, mainly for Mycobacterium avium complex. Very few complications were noted., Conclusion: The number of cases of NTM disease has almost doubled between 2000-2004 compared with between 1990-1999, with more invasive cases seen in the past 4 years. The significance of this important rise in numbers is still unclear. Resolution of NTM adenitis is higher with complete surgical excision of affected lymph nodes. Moreover, given the proportion of PPD > or = 10mm among those tested, a pan-Canadian study assessing the incidence of NTM disease compared with tuberculosis is required to determine if a change in the recommendations for PPD positivity is needed.

Unlabelled: Population-based studies may give results different from randomized clinical trials assessing the efficacy of antibiotics., Objective: To determine the effectiveness of amoxicillin, azithromycin, cefprozil and clarithromycin in the treatment of acute otitis media (AOM) in children., Methods: Using Quebec Health Insurance databases (RAMQ), we selected a cohort of children aged < or = 6 years, with a first episode of AOM between 1999 and 2002. The index AOM was defined as a medical service claim with a diagnosis of AOM and an antibiotic dispensation in the following 72 hours. Failures were defined as a new antibiotic dispensation, a hospitalization or outpatient visit for complications related to AOM in the 30 days after the index AOM. Data were analyzed using logistic regression., Results: Overall, 12,693 failures occurred among 60,513 first episodes of AOM. Azithromycin was the only antibiotic that was associated with a decreased risk of failure overall, when compared to amoxicillin (OR 0.88, 95% CI: 0.82, 0.94). However in the first 3 days of treatment (n = 680), azithromycin was more associated with treatment failure (OR 1.6, 95% CI: 1.3, 2.0). Compared to amoxicillin, post-therapy failures (n = 9387) were more likely to occur with cefprozil (OR 1.2, 95%CI: 1.2, 1.3) but were less with azithromycin (OR 0.8 95% CI: 0.8, 0.9)., Conclusions: Azithromycin had the lowest risk of failure 30 days after the onset of treatment but an increased risk of failure during the first few days of treatment. Amoxicillin remains an effective first-line drug for treating first AOM episodes., (Copyright 2004 John Wiley & Sons, Ltd.)

Background: Acute otitis media (AOM) is one of the most common infectious diseases of childhood and the most frequent indication for antibiotic use in children. Aim To better understand the prescribing patterns and appropriateness of AOM therapy., Methods: We investigated a historical cohort of children aged < or = 6 years who had a first AOM episode between June 1999 and June 2002, using the Régie de l'assurance maladie du Quebec (RAMQ) administrative databases. Conformity of prescription was based on the consensus guidelines on AOM treatment from the Drug-resistant Streptococcus pneumoniae Therapeutic Working Group. These recommendations suggested amoxicillin as the first-line drug, and amoxicillin-clavulanic acid or cefuroxime for children who had received antibiotics in the previous month. Data were analysed using descriptive statistics, chi(2) test and logistic regression., Results: During the study period, 60 513 children < or = 6 years of age experienced their first AOM episode with a mean age of 2.6 years. They were seen by 4708 physicians [87% general practitioners (GPs), 9% paediatricians, and 3% ENT specialists]. Amoxicillin was the antibiotic that was prescribed the most (43%), followed by cefprozil and azithromycin. Overall, 42% of physicians adhered to antibiotic guideline recommendations. Compared with GPs, paediatricians were almost as likely to prescribe in conformity with the consensus guidelines, whereas ENT specialists were 50% less likely to prescribe an antibiotic recommended by the guidelines., Conclusion: Continuing medical education is necessary to ensure appropriate adherence to antibiotic guidelines.

Unlabelled: Infections caused by influenza virus lead to an excess rate of hospitalization of children during winter months. Current recommendations for vaccination target only children >6 months who belong to specific risk groups., Objective: To identify possible benefits of universal influenza vaccination, this study aims to determine characteristics of children hospitalized at the Montreal Children's Hospital (MCH) because of an infection attributable to influenza virus as well as risk factors associated with hospitalization., Methods: We retrospectively reviewed records of all children with a laboratory-proven diagnosis of influenza seen at MCH between April 1, 1999, and April 1, 2002. Data were analyzed using the Student t test and logistic regression., Results: We identified 182 patients hospitalized because of influenza and 114 patients who were not. Admission diagnoses were suspected sepsis (31%), lower respiratory tract infections (27%), and asthma or bronchiolitis (15%). Mean age of hospitalized patients was 26.1 month (median: 12 months), which was similar to that of patients not hospitalized, and 34% were <6 months. Seventy percent of those hospitalized did not have any underlying medical disorder and only 18% (33) were vaccine candidates according to current recommendations. Of the latter, less than half had been vaccinated. Factors associated with hospitalization were age <12 months (odds ratio [OR]: 2.3; 95% confidence interval [CI]: 1.1-4.8), male gender (OR: 1.9; 95% CI: 1.0-3.7), dehydration (OR: 4.3; 95% CI: 1.2-16.0), and decreased oxygen saturation (OR: 32.1; 95% CI: 4.1-249)., Conclusions: Considering that the majority of children hospitalized for influenza do not belong to the specific risk groups targeted by current recommendations, and that one third are <6 months of age, the target population for vaccination needs to be reexamined. Extending vaccination to all young children, to additional high-risk groups, and to pregnant women has potential to reduce the impact of influenza on children.

Invasive Streptococcus pneumoniae infections in children are associated with serious consequences in terms of morbidity and mortality. The main objective of the study was to determine if invasive infections caused by penicillin-resistant Streptococcus pneumoniae (PRSP) differed in clinical presentation, outcome, risk factors, or cost from those caused by penicillin-susceptible strains (PSSP) in children. All patients aged 18 or less with invasive Streptococcus pneumoniae infections admitted to two teaching hospitals in Montreal between 1989 and 1998 were included in the study. We present a case-control study in which for each index case of PRSP, 3 controls with PSSP infections were matched for age, sex, and site of infection. One hundred and forty-four patients were included in the analysis (36 cases, 108 controls). There was no difference between the two groups in terms of initial clinical presentation (vital signs, laboratory results) or total length of stay. Mortality was 2.7% in both groups. Hospital antibiotic cost was higher in the PRSP group (211 Canadian dollars (CAD) vs. 74 CAD; P=0.02). Antibiotic consumption in the preceding month was significantly associated with PRSP infection. Underlying diseases or day-care attendance were not shown to be significant risk factors for acquiring invasive PRSP infection. There were no differences between invasive infections caused by PRSP and PSSP in terms of clinical presentation, morbidity or mortality in a paediatric population.

The performance of a lateral-flow immunoassay, the QuickVue Influenza Test, for detection of influenza A and B viruses in comparison with that of cell culture was evaluated by using nasopharyngeal aspirates, in viral transport medium, from children with respiratory tract infections. The sensitivity and specificity were 79.2 and 82.6%, respectively.

Multiple complications of varicella have been described. Musculoskeletal complications (osteomyelitis, septic arthritis, and necrotizing fasciitis) as well as neurologic complications (ataxia, encephalitis, and transverse myelitis) are well-known. We describe the cases of 2 children, ages 18 months and 5 years, who were admitted recently to 2 pediatric hospitals in Montreal with a resolving varicella, abdominal and lumbar pain, and a refusal to walk and in whom a diagnosis of epidural abscess caused by group A streptococcus (GAS) was established. No previous case of epidural abscess caused by GAS in the context of varicella has been reported. Epidural abscesses are rare in pediatrics and are caused mainly by hematogenous spread of Staphylococcus aureus. The diagnosis in pediatrics is challenging because it is rare and does not present as classically as in adults. The prognosis is related to the presence of neurologic deficits before surgery and to the rapidity with which the diagnosis and the intervention are made. These cases highlight a new clinical association in children of epidural abscess caused by GAS and varicella. An early clinical diagnosis requires a high index of suspicion when back or abdominal pain with or without neurologic signs and symptoms occurs during or soon after varicella.

New ketolides such as ABT-773 are a promising group of antibiotics in an era of increasing antibiotic resistance. We tested 704 invasive strains of Streptococcus pneumoniae collected from 1990 to 1998. Overall resistance was 8.3, 4.6, 4.5 and 3.6% for penicillin, cefuroxime, erythromycin and clarithromycin, respectively. By using a recommended breakpoint for susceptibility of <0.5 mg/L, no strains showed reduced susceptibility to ABT-773. ABT-773 was very active against all penicillin-resistant strains (MIC > 2 mg/L, with a mean geometric mean <0.06 mg/L), and against all 33 erythromycin-resistant strains, irrespective of the mode of resistance [mef- or erm(B)-mediated]. ABT-773 is a very active and promising agent against invasive strains of S. pneumoniae, including multiresistant strains.

The present study tested if a positive modulator of AMPA-type glutamate receptors would counteract the behavioral effects of a drug that enhances the release of dopamine. BDP-29, a compound shown to increase AMPA receptor-mediated synaptic responses in hippocampal slices, markedly attenuated the amount of stereotypic rearings seen in rats after methamphetamine injections. These results suggest that AMPA receptor modulators ameliorate certain aberrant, dopamine-related behaviors and hence may be of interest with regard to schizophrenia.

The effects of a recently synthesized benzoyl-piperidine drug that enhances currents mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)-type glutamate receptors were tested on monosynaptic and polysynaptic responses in hippocampal slices of the rat. Stimulation of perforant path inputs to the dentate gyrus evoked extracellular responses in field CA1 that had latencies and laminar profiles indicating that they were relayed through the trisynaptic intrahippocampal circuit. Under control conditions, trisynaptic field excitatory postsynaptic potentials did not show larger paired-pulse facilitation than monosynaptic responses and failed to exhibit frequency facilitation. Low concentrations of picrotoxin greatly enhanced trisynaptic responses and, under these conditions, frequency facilitation was obtained. Benzoyl-piperidine-12 (250 microM) had a three-fold greater effect on the amplitude of trisynaptic responses than on monosynaptic field excitatory postsynaptic potentials, indicating that the drug's effect is amplified across the successive stages of a polysynaptic circuit. The AMPA receptor modulator did not change the frequency characteristics of monosynaptic potentials and had only a modest influence on those of the trisynaptic response. The effect of benzoyl-piperidine-12 on trisynaptic responses was significantly greater when GABAergic inhibition was partially blocked with picrotoxin; the GABA blocker did not alter the effects of benzoyl-piperidine-12 on monosynaptic responses. These results indicate that centrally active AMPA receptor modulators are likely to have a greater influence on brain operations involving long chains of connections than on those mediated by simple reflex-like circuits, and will vary markedly in their effects depending upon the excitability of local interneurons.