Impact of Deep Learning Denoising Algorithm on Diffusion Tensor Imaging of the Growth Plate on Different Spatial Resolutions.

To assess the impact of a deep learning (DL) denoising reconstruction algorithm applied to identical patient scans acquired with two different voxel dimensions, representing distinct spatial resolutions, this IRB-approved prospective study was conducted at a tertiary pediatric center in compliance with the Health Insurance Portability and Accountability Act. A General Electric Signa Premier unit (GE Medical Systems, Milwaukee, WI) was employed to acquire two DTI (diffusion tensor imaging) sequences of the left knee on each child at 3T: an in-plane 2.0 × 2.0 mm2 with section thickness of 3.0 mm and a 2 mm3 isovolumetric voxel; neither had an intersection gap. For image acquisition, a multi-band DTI with a fat-suppressed single-shot spin-echo echo-planar sequence (20 non-collinear directions; b-values of 0 and 600 s/mm2) was utilized. The MR vendor-provided a commercially available DL model which was applied with 75% noise reduction settings to the same subject DTI sequences at different spatial resolutions. We compared DTI tract metrics from both DL-reconstructed scans and non-denoised scans for the femur and tibia at each spatial resolution. Differences were evaluated using Wilcoxon-signed ranked test and Bland-Altman plots. When comparing DL versus non-denoised diffusion metrics in femur and tibia using the 2 mm × 2 mm × 3 mm voxel dimension, there were no significant differences between tract count (p = 0.1, p = 0.14) tract volume (p = 0.1, p = 0.29) or tibial tract length (p = 0.16); femur tract length exhibited a significant difference (p < 0.01). All diffusion metrics (tract count, volume, length, and fractional anisotropy (FA)) derived from the DL-reconstructed scans, were significantly different from the non-denoised scan DTI metrics in both the femur and tibial physes using the 2 mm3 voxel size (p < 0.001). DL reconstruction resulted in a significant decrease in femorotibial FA for both voxel dimensions (p < 0.01). Leveraging denoising algorithms could address the drawbacks of lower signal-to-noise ratios (SNRs) associated with smaller voxel volumes and capitalize on their better spatial resolutions, allowing for more accurate quantification of diffusion metrics.

Pediatric RSV-Associated Hospitalizations Before and During the COVID-19 Pandemic.

Importance: Respiratory syncytial virus (RSV) is a leading cause of pediatric hospitalizations. Objective: To describe the epidemiology and burden of RSV-associated hospitalizations among children and adolescents in Canadian tertiary pediatric hospitals from 2017 to 2022, including changes during the COVID-19 pandemic. Design, Setting, and Participants: This cross-sectional study was conducted during 5 RSV seasons (2017-2018 to 2021-2022) at 13 pediatric tertiary care centers from the Canadian Immunization Monitoring Program Active (IMPACT) program. Hospitalized children and adolescents aged 0 to 16 years with laboratory-confirmed RSV infection were included. Main Outcomes and Measures: The proportion of all-cause admissions associated with RSV and counts and proportions of RSV hospitalizations with intensive care unit (ICU) admission, prolonged stay (≥7 days), and in-hospital mortality were calculated overall and by season, age group, and region. Seasonality was described using epidemic curves. RSV hospitalizations for 2021-2022 were compared with those in the prepandemic period of 2017-2018 through 2019-2020. Bonferroni corrections were applied to P values to adjust for multiple statistical comparisons. Results: Among 11 014 RSV-associated hospitalizations in children and adolescents (6035 hospitalizations among male patients [54.8%]; 5488 hospitalizations among patients aged <6 months [49.8%]), 2594 hospitalizations (23.6%) had admission to the ICU, of which 1576 hospitalizations (60.8%) were among children aged less than 6 months. The median (IQR) hospital stay was 4 (2-6) days. The mean (SD) number of RSV-associated hospitalizations during prepandemic seasons was 2522 (88.8) hospitalizations. There were 58 hospitalizations reported in 2020-2021, followed by 3170 hospitalizations in 2021-2022. The proportion of all-cause hospitalizations associated with RSV increased from a mean of 3.2% (95% CI, 3.1%-3.3%) before the pandemic to 4.5% (95% CI, 4.3%-4.6%) in 2021-2022 (difference, 1.3 percentage points; 95% CI, 1.1-1.5 percentage points; corrected P < .001). A significant increase in RSV-associated hospitalizations was found in 2021-2022 for 3 provinces (difference range, 2.5 percentage points; 95% CI, 1.4-3.6 percentage points for Quebec to 2.9 percentage points; 95% CI, 1.4-3.5 percentage points for Alberta; all corrected P < .001). Age, sex, ICU admission, prolonged length of stay, and case fatality rate did not change in 2021-2022 compared with the prepandemic period. Interregional differences in RSV seasonality were accentuated in 2021-2022, with peaks for 1 province in October, 4 provinces in December, and 3 provinces in April, or May. Conclusions and Relevance: This study found that the burden of RSV-associated hospitalizations in Canadian pediatric hospitals was substantial, particularly among infants aged less than 6 months, and RSV hospitalizations increased in 2021-2022 compared with the prepandemic period, while severity of illness remained similar. These findings suggest that RSV preventive strategies for infants aged less than 6 months would be associated with decreased RSV disease burden in children.

LAVA HyperSense and deep-learning reconstruction for near-isotropic (3D) enhanced magnetic resonance enterography in patients with Crohn's disease: utility in noise reduction and image quality improvement.

PURPOSE: This study aimed to compare near-isotropic contrast-enhanced T1-weighted (CE-T1W) magnetic resonance enterography (MRE) images reconstructed with vendor-supplied deep-learning reconstruction (DLR) with those reconstructed conventionally in terms of image quality. METHODS: A total of 35 patients who underwent MRE for Crohn's disease between August 2021 and February 2022 were included in this retrospective study. The enteric phase CE-T1W MRE images of each patient were reconstructed with conventional reconstruction and no image filter (original), with conventional reconstruction and image filter (filtered), and with a prototype version of AIRTM Recon DL 3D (DLR), which were then reformatted into the axial plane to generate six image sets per patient. Two radiologists independently assessed the images for overall image quality, contrast, sharpness, presence of motion artifacts, blurring, and synthetic appearance for qualitative analysis, and the signal-to-noise ratio (SNR) was measured for quantitative analysis. RESULTS: The mean scores of the DLR image set with respect to overall image quality, contrast, sharpness, motion artifacts, and blurring in the coronal and axial images were significantly superior to those of both the filtered and original images (P < 0.001). However, the DLR images showed a significantly more synthetic appearance than the other two images (P < 0.05). There was no statistically significant difference in all scores between the original and filtered images (P > 0.05). In the quantitative analysis, the SNR was significantly increased in the order of original, filtered, and DLR images (P < 0.001). CONCLUSION: Using DLR for near-isotropic CE-T1W MRE improved the image quality and increased the SNR.

Impact of the Withdrawal of Palivizumab Immunoprophylaxis on the Incidence of Respiratory Syncytial Virus (RSV) Hospitalizations Among Infants Born at 33 to 35 Weeks' Gestational Age in the Province of Quebec, Canada: The RSV-Quebec Study.

BACKGROUND: Infants born at 33-35 completed weeks' gestational age (wGA) aged <6 months at the start of or born during respiratory syncytial virus (RSV) season and classified as moderate/high risk of severe RSV disease were included in a palivizumab RSV prophylaxis program in the province of Quebec, Canada, until 2014-2015. We assessed the impact of withdrawal of this indication on lower respiratory tract infection (LRTI)/RSV hospitalizations (H) in this population. METHODS: We conducted a 4-year, retrospective, cohort study in 25 Quebec hospitals (2 seasons with and 2 without palivizumab prophylaxis for moderate- to high-risk infants). Our primary outcome was LRTI/RSV-H incidence. We compared LRTI/RSV-H incidence before (2013-2015; seasons 1 + 2 [S1/2]) and after (2015-2017; S3/4) the change in indication. RESULTS: We identified 6457 33-35 wGA births. LRTI/RSV-H occurred in 105/3353 infants (3.13%) in S1/2 and 130/3104 (4.19%) in S3/4. Among LRTI/RSV-H, 86.4% were laboratory-confirmed RSV-H. Adjusting for sex, wGA, and birth month, S3/4 was significantly associated with increased LRTI/RSV-H incidence (adjusted odds ratio [aOR], 1.36; 95% confidence interval [CI], 1.04-1.76) but not with laboratory-confirmed RSV-H (aOR, 1.19; 95% CI, 0.90-1.58). Mean duration of LRTI/RSV-H was 5.6 days; 22.6% required intensive care unit admission. Comparing S3/4 with S1/2, infant percentage with LRTI/RSV-H classified as moderate/high risk increased from 27.8% to 41.9% (P = .11). CONCLUSIONS: In a province-wide study, we observed a significant increase in LRTI/RSV-H incidence among infants born at 33-35 wGA in the 2 years after withdrawal of RSV prophylaxis.

Thin-Slice Pituitary MRI with Deep Learning-based Reconstruction: Diagnostic Performance in a Postoperative Setting.

Background Achieving high-spatial-resolution pituitary MRI is challenging because of the trade-off between image noise and spatial resolution. Deep learning-based MRI reconstruction enables image denoising with sharp edges and reduced artifacts, which improves the image quality of thin-slice MRI. Purpose To assess the diagnostic performance of 1-mm slice thickness MRI with deep learning-based reconstruction (DLR) (hereafter, 1-mm MRI+DLR) compared with 3-mm slice thickness MRI (hereafter, 3-mm MRI) for identifying residual tumor and cavernous sinus invasion in the evaluation of postoperative pituitary adenoma. Materials and Methods This single-institution retrospective study included 65 patients (mean age ± standard deviation, 54 years ± 10; 26 women) who underwent a combined imaging protocol including 3-mm MRI and 1-mm MRI+DLR for postoperative evaluation of pituitary adenoma between August and October 2019. Reference standards for correct diagnosis were established by using all available imaging resources, clinical histories, laboratory findings, surgical records, and pathology reports. The diagnostic performances of 3-mm MRI, 1-mm slice thickness MRI without DLR (hereafter, 1-mm MRI), and 1-mm MRI+DLR for identifying residual tumor and cavernous sinus invasion were evaluated by two readers and compared between the protocols. Results The performance of 1-mm MRI+DLR in the identification of residual tumor was comparable to that of 3-mm MRI (area under the receiver operating characteristic curve [AUC], 0.89-0.92 vs 0.85-0.89, respectively; P ≥ .09). In the identification of cavernous sinus invasion, the diagnostic performance of 1-mm MRI+DLR was higher than that of 3-mm MRI (AUC, 0.95-0.98 vs 0.83-0.87, respectively; P ≤ .02). Conventional 1-mm MRI (AUC, 0.82-0.83) showed comparable diagnostic performance to 3-mm MRI (AUC, 0.83-0.87) (P ≥ .38). With 1-mm MRI+DLR, residual tumor was diagnosed in 20 patients and cavernous sinus invasion was diagnosed in 14 patients, in whom these diagnoses were not made with 3-mm MRI. Conclusion In the postoperative evaluation of pituitary adenoma, 1-mm slice thickness MRI with deep learning-based reconstruction showed higher diagnostic performance than 3-mm slice thickness MRI in the identification of cavernous sinus invasion and comparable diagnostic performance to 3-mm slice thickness MRI in the identification of residual tumor. © RSNA, 2020 Online supplemental material is available for this article.

Reevaluating immunization delays after red blood cell transfusion.

BACKGROUND: Current American and Canadian guidelines recommend delaying live vaccine immunization by 5 to 6 months after transfusion of red blood cells (RBCs) due to potential interference by serum antibodies. Due to lack of data, the recommendations may be unfounded and prevent valuable vaccination opportunities for children with frequent blood transfusions. The primary aim of this study was to determine measles, mumps, rubella (MMR) vaccine immunogenicity in patients chronically transfused with RBCs. A secondary aim was to quantify vaccine antibodies in RBC donations. STUDY DESIGN AND METHODS: MMR-specific antibodies were quantified in 25 pediatric patients who received both doses of MMR vaccine while on a chronic RBC transfusion program (median, 6.6 years after vaccination). MMR antibodies were also quantified in 30 samples of supernatants from RBC donations. RESULTS: Immunity to each of the MMR components was 68% to 76%. In blood donors born before 1976 (pre-MMR vaccine), 67% of MMR serologies in the supernatants of RBC donations were at the immune level versus 7% in blood donors born after 1976. CONCLUSION: This is the first study of the impact of RBC transfusions on MMR vaccine immunogenicity. Although lower than in the literature (immunity rates, ≥90%), the results show a high rate of immunogenicity of the MMR vaccine in chronically transfused patients. Additionally, results suggest that MMR antibody content in transfusions will continue to decrease with time. Weighing the risks and benefits of disease prevention in a vulnerable population, a reevaluation of immunization delays after RBC transfusions is called for.

Comparing accuracy and reproducibility of sequential and Hadamard-encoded multidelay pseudocontinuous arterial spin labeling for measuring cerebral blood flow and arterial transit time in healthy subjects: A simulation and in vivo study.

PURPOSE: To compare performance of sequential and Hadamard-encoded pseudocontinuous arterial spin labeling (PCASL). MATERIALS AND METHODS: Monte Carlo simulations and in vivo experiments were performed in 10 healthy subjects. Field strength and sequence: 5-delay sequential (5-del. Seq.), 7-delay Hadamard-encoded (7-del. Had.), and a single-delay (1-del.) PCASL, without and with vascular crushing at 3.0T. The errors and variations of cerebral blood flow (CBF) and arterial transit time (ATT) from simulations and the CBF and ATT estimates and variations in gray matter (GM) with different ATT ranges were compared. Pairwise t-tests with Bonferroni correction were used. RESULTS: The simulations and in vivo experiments showed that 1-del. PCASL underestimated GM CBF due to insufficient postlabeling delay (PLD) (37.2 ± 8.1 vs. 47.3 ± 8.5 and 47.3 ± 9.0 ml/100g/min, P ≤ 6.5 × 10-6 ), while 5-del. Seq. and 7-del. Had. yielded comparable GM CBF (P ≥ 0.49). 5-del. Seq. was more reproducible for CBF (P = 4.7 × 10-4 ), while 7-del. Had. was more reproducible for ATT (P = 0.033). 5-del. Seq. was more prone to intravascular artifacts and yielded lower GM ATTs compared to 7-del. Had. without crushing (1.13 ± 0.18 vs. 1.23 ± 0.13 seconds, P = 2.3 × 10-3 ), but they gave comparable ATTs with crushing (P = 0.12). ATTs measured with crushing were longer than those without crushing (P ≤ 6.7 × 10-4 ), but CBF was not affected (P ≥ 0.16). CONCLUSION: The theoretical signal-to-noise ratio (SNR) gain through Hadamard encoding was confirmed experimentally. For 1-del., a PLD of 1.8 seconds is recommended for healthy subjects. With current parameters, 5-del. Seq. was more reproducible for CBF, and 7-del. Had. for ATT. Vascular crushing may help reduce variations in multidelay experiments without compromising tissue CBF or ATT measurements. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1119-1132.

Cardio-respiratory Events and Inflammatory Response After Primary Immunization in Preterm Infants < 32 Weeks Gestational Age: A Randomized Controlled Study.

BACKGROUND: Inflammation may depress respiration in neonates. This study aimed to establish a link between postimmunization inflammation and cardio-respiratory events (CREs). METHODS: Randomized double-blind controlled study of infants born < 32 weeks gestation receiving the 2 months vaccine, which comprised diphtheria and tetanus toxoids and acellular pertussis adsorbed combined with inactivated poliomyelitis vaccines and Haemophilus b conjugate and the pneumococcal conjugate 10-valent vaccines. Infants were randomized to ibuprofen treatment or a placebo group (n = 28/group). C-reactive protein (CRP) and prostaglandins E2 (PgE2) levels were assessed before and after immunization. CREs were recorded for 72 hours. Heart rate variability was assessed by polysomnography. RESULTS: In the placebo group, immunization was associated with significantly increased CRP levels and an increase in CRE (8.6 ± 11.1 before versus 14.0 ± 12.8 after), which did not reach statistical significance (P = 0.08), and no change in PgE2. The increase in CRP was correlated with changes in CRE (r = 0.4: P < 0.05). In the ibuprofen group, immunization significantly increased CRP levels but was not associated with change in CRE (6.7 ± 7.7 before versus 6.8 ± 9.7 after) and PgE2 levels. Comparing the groups, variation in CRE (ΔCRE before versus after immunization) was significantly lower in the ibuprofen group (0.1 ± 7.9 versus 5.4 ± 10.0 ΔCRE; P < 0.05). CONCLUSION: The first immunization of infants born < 32 weeks was associated with an increase in CRP. Ibuprofen treatment significantly attenuated the variation (Δ) in CRE following first immunization in these infants but the current study could not demonstrate an impact on CRP and PgE2 levels. The impact of anti-inflammatory treatment on antigenicity must be evaluated before their clinical use aiming at reducing CRE after immunization in preterm infants.

Characterization of multiple cytomegalovirus drug resistance mutations detected in a hematopoietic stem cell transplant recipient by recombinant phenotyping.

Cytomegalovirus resistance to antivirals is a major problem in transplant recipients. We evaluated the impact of five mutations (A594V, L595F, and E655K in the UL97 gene and V526L and E756K in the UL54 gene), detected in a blood sample from a stem cell transplant recipient, on drug susceptibilities and replicative capacities of recombinant viruses.

Randomized, multicenter trial of a single dose of AS03-adjuvanted or unadjuvanted H1N1 2009 pandemic influenza vaccine in children 6 months to <9 years of age: safety and immunogenicity.

BACKGROUND: During the 2009-2010 influenza pandemic, we evaluated the immunogenicity and safety of different H1N1 2009 pandemic influenza vaccines delivering various viral hemagglutinin (HA) doses with or without AS03 (a tocopherol oil-in-water emulsion-based adjuvant system) in children (NCT00976820). METHODS: Three hundred twenty-two healthy children 6 months to <9 years of age were randomized to receive 2 doses of nonadjuvanted (15 µg or 7.5 µg HA) or adjuvanted vaccine (3.75 µg HA/AS03A or 1.9 µg HA/AS03B), 21 days apart. Blood samples before and after each dose were tested for immune responses using hemagglutination inhibition and microneutralization assays. Safety assessments were done up to day 385. RESULTS: The first dose of both AS03-adjuvanted vaccines elicited strong immune responses (seroprotection rates: 98.3%/99.0%; seroconversion rates: 94.9%/97.0%; geometric mean fold rises: 36.2/33.6), which were higher post-dose 2 (seroprotection rate: 100.0%/100%; seroconversion rate: 100.0%/98.8%; geometric mean fold rise: 157.1/151.6), meeting European regulatory criteria on days 21 and 42. The nonadjuvanted 15 µg HA vaccine also met the regulatory criteria after each dose; the 7.5 µg HA vaccine met them only post-dose 2. Six months post-dose 1, all vaccines except the nonadjuvanted 7.5 µg HA vaccine met European regulatory criteria. Neutralizing antibody response paralleled the hemagglutination inhibition immune response after each dose. Pain at the injection site, lasting 2-3 days, was more common following adjuvanted than nonadjuvanted vaccination. CONCLUSIONS: AS03-adjuvanted H1N1 2009 pandemic influenza vaccine (3.75 µg or 1.9 µg HA), administered as 2 doses, was highly immunogenic, induced long-term immune response to 6 months, with a clinically acceptable safety profile in children aged 6 months to <9 years of age.

Automatic segmentation of spinal cord MRI using symmetric boundary tracing.

We develop an adaptive active contour tracing algorithm for extraction of spinal cord from MRI that is fully automatic, unlike existing approaches that need manually chosen seeds. We can accurately extract the target spinal cord and construct the volume of interest to provide visual guidance for strategic rehabilitation surgery planning.

The rise of the rats: A growing paediatric issue.

Rat bite fever (RBF), a systemic infection of Streptobacillus moniliformis or Spirillum minus characterized by fever, arthralgias and petechial-purpuric rash on the extremities, carries a mortality rate of 7% to 10% if untreated. In Canada, one adult and two paediatric cases of RBF have been reported since 2000. In recent years, pet rats have become quite popular among children, placing them at an increased risk for RBF. Thus, paediatricians need to be more wary of the potential for RBF in their patients. In the present report, a culture-confirmed case of RBF and two additional cases of suspected infection are described.

Antibiotic prophylaxis for childhood urinary tract infection: a national survey.

AIMS: To describe attitudes of paediatricians and paediatric nephrologists regarding antibiotic prophylaxis for urinary tract infection (UTI) and determine the factors associated with its use. METHOD: A self-administered questionnaire was mailed to Canadian paediatricians (1136) and paediatric nephrologists (42). RESULTS: The response rate was 58.1% (684 physicians); 436 who had made a decision about antibiotic prophylaxis for childhood UTI in the previous year were included in the analysis. Of these, 407 (93.3%) were certified in paediatrics and 29 (6.7%) were paediatric nephrologists. Most respondents prescribed prophylaxis for children with grade III-V vesicoureteral reflux (VUR) (96.5%-98%); 69.8 and 92.8% prescribed it for children with grades I and II VUR, respectively. Factors significantly associated with use of prophylaxis for children with grade I VUR were frequency of decision-making about prophylaxis, city size and province. Fifteen percent of physicians felt that their practice regarding antibiotic prophylaxis for children with VUR was evidence based. A hundred one respondents (24.3%) prescribed prophylaxis for infants with a first febrile UTI in the absence of VUR. Nineteen percent felt that their practice regarding antibiotic prophylaxis for these infants was evidence based. Prescription of prophylaxis for children >12 months with recurrent UTI in the absence of VUR was influenced by frequency of pyelonephritis (88.5% of respondents) and presence of voiding dysfunction (53.8%). Nine percent of physicians felt that their practice for these children was evidence based. CONCLUSION: Opinions of Canadian paediatricians and paediatric nephrologists regarding antibiotic prophylaxis for UTI in children vary widely, probably because of the paucity of solid evidence about prophylaxis.

Measuring the Impact of Rotavirus Acute Gastroenteritis Episodes (MIRAGE): A prospective community-based study.

BACKGROUND: Current assessments of the burden of rotavirus (RV)-related gastroenteritis are needed to evaluate the potential benefits of RV immunization interventions. The objective of the present study was to characterize the burden of RV gastroenteritis among children presenting in outpatient settings with gastroenteritis. METHODS: Between January and June 2005, 395 children younger than three years of age presenting with gastroenteritis symptoms (at least three watery or looser-than-normal stools, or forceful vomiting within the previous 24 h period) were recruited from 59 Canadian clinics and followed for two weeks. Stool specimens were tested for the RV antigen. Gastroenteritis-related symptoms, health care utilization, parental work loss and other cases of gastroenteritis in the household were assessed by questionnaires and daily symptom cards that were completed by caregivers. RESULTS: Of 336 conclusive test results, 55.4% were RV positive (RV+). In addition to diarrhea, 67.2% and 89.3% of RV+ children experienced fever or vomiting, respectively. Compared with RV-negative (RV-) children, RV+ children were more likely to experience the three symptoms concurrently (57.0% versus 26.7%; P<0.001), to be hospitalized (12.9% versus 3.9%; P=0.008) and to induce parental work loss (53.8% versus 37.3%; P=0.003). The median duration of gastroenteritis was eight days for RV+ children (nine days for RV- children). Additional cases of gastroenteritis were present in 46.8% of households in the RV+ group (51.3% of households in the RV- group). CONCLUSIONS: RV gastroenteritis cases were more severe than other gastroenteritis cases, were hospitalized more often and were associated with considerably more work loss.

Prevalence of positive tuberculin skin tests in foreign-born children.

AIMS: To evaluate the prevalence of positive tuberculin skin tests (TST) in internationally adopted and immigrant children. To identify risk factors for positive TST in these populations. METHODS: The study was a retrospective medical record review in a tertiary care pediatric hospital. All children evaluated at the International Adoption and Immigrant Health Clinic of CHU Sainte-Justine in Montreal, Canada, between 01-01-1998 and 31-12-2001 were included. Demographic and anthropometrical data, BCG vaccination, TST, chest X-ray results and treatment were extracted from the medical records of the patients and analyzed. Positive TST was defined as induration = 10 mm, 48 to 72 hours after injection of five tuberculin units of purified protein derivate. RESULTS: Our population included 670 children: 112 immigrants and 558 adoptees. Median age was 6.9 years for immigrants and 1.1 years for adopted children. Overall incidence of positive TST was 12.2% in our cohort: 31% in the immigrant and 8% in the adopted children groups. There was one case of active tuberculosis. Older age on arrival in Canada and BCG vaccination were identified as risk factors for positive TST in our multivariate model. For each one-year increase in age on arrival in Canada, there was a 1.2 times greater risk for positive TST. CONCLUSIONS: Latent tuberculosis is a frequent problem in foreign-born children. The higher incidence in immigrant children can be explained by older age on arrival.

Surveillance for influenza admissions among children hospitalized in Canadian immunization monitoring program active centers, 2003-2004.

OBJECTIVES: Influenza is a common childhood infection that may result in hospitalization. Our objectives were to (1) determine characteristics of children hospitalized for influenza and disease manifestations and (2) obtain baseline data before implementation of new recommendations for routine immunization of young children and their caretakers against influenza. METHODS: All of the children hospitalized with laboratory-confirmed influenza at 9 Canadian tertiary care hospitals during the 2003-2004 influenza season were identified from virology laboratory reports, and their charts were reviewed. RESULTS: There were 505 children admitted because of influenza. Fifty-seven percent were < 2 years old. Previously healthy children accounted for 58% of all of the cases. Pulmonary and neurologic disorders were the most common underlying chronic conditions. Fever and cough were the most frequent manifestations. Seizures occurred in 9% of cases. Serious complications included myocarditis (2), encephalopathy (6), and meningitis (1). There were 3 influenza-related deaths. Mean duration of hospitalization was 5.3 days. Twelve percent of children required ICU admission, and 6% required mechanical ventilation. Antibiotic therapy was administered in 77% of cases, and 7% received anti-influenza drugs. Information on influenza vaccination was available for 84 of 154 children identified as vaccine candidates. Twenty two had received vaccine, but only 7 children had been fully immunized > 14 days before the onset of illness. CONCLUSIONS: Healthy young children and children with chronic conditions are at risk for serious illness with influenza. Ongoing surveillance is needed to evaluate the impact of changing immunization recommendations on the burden of influenza illness in children.

Palivizumab use among children with congenital heart disease in Quebec: Impact of Canadian guidelines on clinical practice.

BACKGROUND: Palivizumab has been shown to reduce the risk of hospitalization caused by respiratory syncytial virus in children with congenital heart disease (CHD). Guidelines published in 2003 by the Canadian Paediatric Society (CPS) stated that children younger than 24 months with hemodynamically significant CHD should be considered for up to five monthly doses of palivizumab during the winter season. OBJECTIVE: To assess the impact of CPS guidelines on the use of palivizumab in children with CHD. METHODS: Clinical information was reviewed on all patients with CHD who were prescribed palivizumab in 2002-2003 and 2003-2004 and who were followed by one of four paediatric cardiovascular programs in the province of Quebec. RESULTS: Palivizumab was prescribed to 45 children in 2002-2003 and to 146 children in 2003-2004. The number of children receiving more than five doses increased from 10 of 45 (22%) in 2002-2003 to 57 of 128 (45%) in 2003-2004 (P=0.008). One hundred seventeen of 146 children (80%) receiving palivizumab in 2003-2004 met the CPS guidelines versus 38 of 45 children (84%) in 2002-2003 (ie, before the guidelines were published) (P=0.66). Patients not meeting CPS criteria were older than 24 months at the time of the first dose, had hemodynamically insignificant CHD or had lesions adequately corrected by surgery. CONCLUSIONS: The number of children with CHD receiving palivizumab prophylaxis increased significantly following the publication of CPS guidelines. The majority of children were eligible for palivizumab according to the current CPS criteria. More patients received more than five doses in 2003-2004 than in 2002-2003.

Invasive Haemophilus influenzae type b infections in vaccinated and unvaccinated children in Canada, 2001-2003.

BACKGROUND: Although vaccination of infants against Haemophilus influenzae type b (Hib) invasive infections is effective and has been routinely available in Canada since 1992, cases of the disease continue to occur. We were interested in determining whether recent cases of Hib infection reflected progressive loss of protection with time since vaccination, increasing nonacceptance of vaccination or a deleterious effect of coadministration of recently introduced vaccines such as those for pneumococcal and meningococcal conjugates and hepatitis B. We report on the causes of Hib infections among vaccinated and unvaccinated children between 2001 and 2003 in Canada. METHODS: Through our established network of 12 pediatric tertiary care hospitals we actively searched for cases in each centre by reviewing daily admissions and laboratory reports, visiting the wards and checking discharge diagnosis codes. Culture-confirmed cases were summarized by nurse monitors using a standardized reporting system. RESULTS: We identified 29 cases during the 3 years: 16 in 2001, 10 in 2002 and 3 in 2003. Half of the 29 patients had meningitis. Hib infection was more common among children less than 6 months of age (11 cases) and in boys (20 cases). Two deaths occurred (7% case-fatality ratio). A total of 20 children had received no or incomplete primary vaccination because of parental refusal (7 cases), because they were too young to have completed the primary series (11 cases, including 1 in which parental refusal was also a factor) or because of delays in completing the primary series (2 cases); the vaccination history was uncertain in the remaining case. Infection despite primary vaccination occurred in 9 children: 2 previously healthy children and 7 who were immunocompromised or who had a predisposing condition. None of the cases identified in 2003 involved children who had received any of the newly introduced vaccines. INTERPRETATION: Invasive Hib infections remain rare in Canada, with most cases occurring in children too young to have completed the primary series. Protection after vaccination appears to extend into later childhood and does not appear to be diminished by coadministration of newer infant vaccines.

A pilot study to evaluate the pharmacokinetics of sibutramine in healthy subjects under fasting and fed conditions.

PURPOSE: The purpose of this study was to characterize the food effect on the pharmacokinetics of sibutramine and its pharmacologically active metabolites. METHODS: This was an open label, single dose, crossover study completed by six healthy males. A single dose of sibutramine 15 mg was administered orally under fasting and fed conditions. Plasma concentrations of sibutramine and its metabolites were determined by LC/MS/MS: Non-compartmental pharmacokinetics and statistical analysis were performed using SAS. RESULTS: The food intake increased significantly AUCs and C(max) of sibutramine and its M1 metabolite, but did not affect M2 metabolite. When sibutramine was administered with food, the T(max) was delayed by 2 to 4 hours for sibutramine, M1 and M2 metabolites as stated in the literature. CONCLUSIONS: The results of this study indicate that sibutramine is measurable using a sensitive bioanalytical method. In contrast with what is reported in the product monograph, this study demonstrated that the bioavailability of sibutramine and M1 metabolite was significantly increased with administration with food. The results confirmed lack of food effect on the pharmacokinetics of M2 metabolite. These relatively large food effect observed for sibutramine and M1 metabolite, could have implication for the efficacy and safety of the drug.

The Pediatric Investigators Collaborative Network on Infections in Canada study of predictors of hospitalization for respiratory syncytial virus infection for infants born at 33 through 35 completed weeks of gestation.

BACKGROUND: Infants born at 33 through 35 completed weeks of gestation (33-35GA) are at risk for severe respiratory syncytial virus (RSV) infection, and palivizumab prophylaxis lowers hospitalizations for RSV infection by as much as 80%. The 33-35GA cohort comprises 3-5% of annual births; thus expert panels recommend limiting prophylaxis to situations in which frequency or health care impact of RSV infection is high. This study sought to identify independent risk factors for hospitalization for RSV infection. METHODS: This was a multicenter, prospective, observational cohort study of 33-35GA infants followed through their first RSV season (2001/2002 or 2002/2003). Baseline data were collected by interview with parents and review of medical records. Respiratory tract illnesses were identified by monthly phone calls, and medical records were reviewed for emergency room visits or hospitalizations. Risk factors were determined by stepwise logistic regression. RESULTS: Of 1,860 enrolled subjects, 1,832 (98.5%) were followed for at least 1 month, and 1,760 (94.6%) completed all follow-ups. Of 140 (7.6%) subjects hospitalized for respiratory tract illnesses, 66 infants had proven RSV infection. Independent predictors for hospitalization for RSV infection were: day-care attendance (odds ratio, 12.32; 95% confidence interval, 2.56, 59.34); November through January birth (odds ratio, 4.89; 95% confidence interval, 2.57, 9.29); preschool age sibling(s) (odds ratio, 2.76; 95% confidence interval, 1.51, 5.03); birth weight <10th percentile (odds ratio, 2.19; 95% confidence interval, 1.14, 4.22); male gender (odds ratio, 1.91; 95% confidence interval, 1.10, 3.31); > or = 2 smokers in the home (odds ratio, 1.87; 95% confidence interval, 1.07, 3.26); and households with >5 people, counting the subject (odds ratio, 1.79; 95% confidence interval, 1.02, 3.16). Family history of eczema (odds ratio, 0.42; 95% confidence interval, 0.18, 0.996) was protective. CONCLUSIONS: Specific host/environmental factors can be used to identify which 33-35GA infants are at greatest risk of hospitalization for RSV infection and likely to benefit from palivizumab prophylaxis.