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Competing Interests: Y. Khitri et C. Quach déclarent n’avoir aucun lien d’intérêts. A. Mekinian déclare des liens ponctuels avec LFB, Genzyme, Chugai. N. Abisror déclare des liens ponctuels avec Genzyme. F. Chasset déclare des liens ponctuels avec GSK. O. Fain déclare des liens ponctuels avec Shire, Behring, GSK, Pfizer, Novartis.

Objective: Although healthcare-associated (HA) viral respiratory infections (VRIs) are common in pediatrics, no benchmark for comparison exists. We aimed to determine, compare, and assess determinants of unit-specific HA-VRI incidence rates in 2 children's hospitals., Methods: This study was a retrospective comparison of prospective cohorts. The Montreal Children's Hospital and the Cohen Children's Medical Center of New York perform prospective surveillance for HA-VRI using standardized definitions that require the presence of symptoms compatible with VRI and virus detection. Cases detected between April 1, 2010, and March 31, 2013, were identified using surveillance databases. Annual incidence rates were calculated, and a generalized estimating equation model was used to assess determinants of HA-VRI rates., Results: The overall HA-VRI rate during the 3-year study period was significantly higher at Montreal Children's Hospital than that at Cohen Children's Medical Center of New York (1.91 vs 0.80 per 1000 patient-days, respectively; P < .0001). Overall, the HA-VRI incidence rate was lowest in the neonatal intensive care unit. Rates in the pediatric intensive care, oncology, and medical/surgical units were similar. The most common etiology of HA-VRI at both institutions was rhinovirus (49% of cases), followed by parainfluenza virus and respiratory syncytial virus. Hospitals with less than 50% single rooms had HA-VRI rates 1.33 (95% confidence interval, 1.29-1.37) times higher than hospitals with more than 50% single rooms for a given unit type., Conclusions: HA-VRI rates were substantial but different among 2 children's hospitals. Future studies should examine the effect of HA-VRI and evaluate best practices for preventing such infections.

Background: We sought to determine if immune disorders early in life were associated with the later risk of Guillain-Barré syndrome, a neurological disorder thought to be infection-related., Methods: We conducted a longitudinal cohort study with 16 108 819 person-years of follow-up for a population of 1 108 541 parous women in Quebec, Canada (1989-2014). The outcome was Guillain-Barré syndrome. We identified women with potential risk factors for future Guillain-Barré syndrome, including immune-mediated and rheumatological diseases, cancer, transfusion, surgical procedures and pregnancy-specific disorders. We estimated hazard ratios (HR) and 95% confidence intervals (CI) for the association of risk factors with later onset of Guillain-Barré syndrome, adjusted for personal characteristics of women., Results: The overall incidence of Guillain-Barré syndrome was 1.42 per 100 000 person-years. Incidence was higher for women with immune-mediated (8.79 per 100 000 person-years) and rheumatological disorders (9.84 per 100 000 person-years), transfusion (4.41 per 100 000 person-years), and preeclampsia (2.62 per 100 000 person-years). Immune-mediated disorders were associated with six times the risk of Guillain-Barré syndrome (HR 6.57, 95% CI 3.58 to 12.04), rheumatological disorders with seven times the risk (HR 7.23, 95% CI 3.21 to 16.28), transfusion three times the risk (HR 3.58, 95% CI 1.83 to 6.98) and preeclampsia two times the risk (HR 2.01, 95% CI 1.29 to 3.12). Women with other potential risk factors did not have an increased risk of Guillain-Barré syndrome., Conclusions: Immune-related conditions that occur early in life are associated with an increased risk of Guillain-Barré syndrome. The pathophysiology of Guillain-Barré syndrome may extend beyond infectious triggers., (© The Author 2017; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association)

Background: The evaluation of the effectiveness of undergraduate palliative care education (UPCE) programs is an essential foundation to providing high-quality UPCE programs. Therefore, the implementation of valid evaluation tools is indispensable. Until today, there has been no general consensus regarding concrete outcome parameters and their accurate measurement. The Program in Palliative Care Education and Practice Questionnaire (German Revised Version; PCEP-GR) is a promising assessment tool for UPCE. The aim of the current study was to evaluate the psychometric properties of PCEP-GR and to demonstrate its feasibility for the evaluation of UPCE programs., Methods: The practical feasibility of the PCEP-GR and its acceptance in medical students were investigated in a pilot study with 24 undergraduate medical students at Heinrich Heine University Dusseldorf, Germany. Subsequently, the PCEP-GR was surveyed in a representative sample (N = 680) of medical students in order to investigate its psychometric properties. Factorial validity was investigated by means of principal component analysis (PCA). Reliability was examined by means of split-half-reliability analysis and analysis of internal consistency. After taking into consideration the PCA and distribution analysis results, an evaluation instruction for the PCEP-GR was developed., Results: The PCEP-GR proved to be feasible and well-accepted in medical students. PCA revealed a four-factorial solution indicating four PCEP-GR subscales: preparation to provide palliative care, attitudes towards palliative care, self-estimation of competence in communication with dying patients and their relatives and self-estimation of knowledge and skills in palliative care. The PCEP-GR showed good split-half-reliability and acceptable to good internal consistency of subscales. Attitudes towards palliative care slightly missed the criterion of acceptable internal consistency. The evaluation instruction suggests a global PCEP-GR index and four subscales., Conclusions: The PCEP-GR has proven to be a feasible, economic, valid and reliable tool for the assessment of UPCE that comprises self-efficacy expectation and relevant attitudes towards palliative care.

Purpose: Provide analysis of data identifying the impending mass turnover of Directors and Coordinators of General Surgery residency programs and the potential effect on successful continuing accreditation including the ACGME Next Accreditation System (NAS) and associated self study., Methods: The Association of Residency Coordinators in Surgery, Executive Committee (ARCS EC) anonymously surveyed 254 general surgery Program Coordinators in September/October 2016. This represents 60`% of all the members within the Association of Residency Coordinators in Surgery. Survey was accomplished using SurveyMonkey. Questions included demographics and experience of the Director and Coordinator, accreditation status, significant job stressors, and potential retirements or position changes planned or possible., Results: 153 (60%) respondents completed the survey. Data from the survey indicates that 67% of Program Directors have been in their position less than six (6) years. 34% of Program Coordinators have been in their position less than five (5) years. 56% of coordinators have been on the job less than ten (10) years. Coordinators in 76% of programs reported significant levels of burnout. 59% have considered resigning from their position in the past year. Participants consistently reported increasing responsibilities and expectations combined with declining or inadequate levels of support as sources of job stress. Other contributors to Coordinator burnout were identified as related to the additional ACGME accreditation requirements and salaries not commensurate with workload., Conclusion: This survey represents a sentinel preliminary look at the possible impending manning crisis in general surgery residency program leadership. A Program Director is supported by a Program Coordinators who are burned out and considering a job change. The resultant potential turnover in personnel and loss of collective program knowledge may have devastating ramifications to program accreditation. Subsequent survey of the workforce will evaluate proposed solutions and interventions to prevent this outcome and secure the future success of general surgery programs., (Copyright © 2017 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate whether simulated patient (SP)-based training has comparable efficacy as live patient (LP)-based training in teaching Focused Abdominal Sonography for Trauma (FAST) knowledge and skill competencies to surgical residents., Design: A randomized pretest/intervention/posttest controlled study design was employed to compare the participants' performance in written and practical examinations regarding FAST examination after SP-based versus LP-based training., Setting: University-based general residency program at a single institution., Participants: A total of 29 general surgery residents of various training levels and sonographic experience were recruited by convenience sampling., Results: There was no correlation between subjects' baseline training level or sonographic experience with either the posttest-pretest score difference or the percentage of subjects getting all 4 windows with adequate quality. There was no significant difference between the improvement in written posttest-pretest scores for SP and LP group, which were 33 ± 9.6 and 31 ± 6.8 (p = 0.40), respectively. With regard to performance-based learning efficacy, a statistically higher proportion of subjects were able to obtain all 4 windows with adequate quality among the LP than the SP group (6/8 vs 1/8, p = 0.01)., Conclusion: SP- and LP-based FAST training for surgical residents were associated with similar knowledge-based competency acquisition, but residents receiving LP-based training were better at acquiring adequate FAST windows on live patients. Simulation training appeared to be a valid adjunct to LP practice but cannot replace LP training. Future investigations on how to improve simulation fidelity and its training efficacy for skill-based competencies are warranted., (Copyright © 2017 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Under-immunization refers to a state of sub-optimal protection against vaccine preventable diseases. Vaccine coverage for age may not capture intentional or non-intentional spacing of vaccines in the recommended provincial immunization guidelines. We aimed to identify factors associated with coverage and under-immunization and to determine the number of days during which children were under-immunized during their first 24months of life., Methods: Secondary analysis of children ≤3years recruited through active surveillance for gastroenteritis from three Quebec pediatric emergency departments from 2012 to 2014. Vaccination status for children at least 24months of age was determined using provincial immunization guidelines. Cumulative days under-immunized were calculated for DTaP-VPI-Hib, PCV, MMR, and Men-C-C. Factors associated with up-to-date (UTD) status at 24months of life and for under-immunization ≥6months were analyzed using logistic regression., Results: Of 246 eligible children, 180 (73%) were UTD by 24months of life. The mean cumulative days under-immunized for MMR was 107days, for PCV 209days, for Men-C-C 145days, and for DTaP-VPI-Hib 227days. Overall, 149 children (60%) experienced delay for at least 1 vaccine. Factors associated with both an UTD status at 24months and concurrently associated with being under-immunization ≥6months, included timely initiation of immunization (OR=5.85; 95% CI: 2.80-12.22) and (OR=0.13; 95% CI: 0.07-0.24), failure to co-administer 18-month vaccines (OR=0.15; 95% CI: 0.10-0.21) and (OR=3.29; 95% CI: 2.47-4.39), and having a household with ≥3 children under 18years ((OR=0.50; 0.28-0.86) and (OR=2.99; 1.45-6.22), respectively., Conclusion: Paired with an unexpected low level of coverage at 24months of life, the majority of our cohort also experienced a state of under-immunization for a least one vaccine. Estimates of coverage do not capture intentional or non-intentional gaps in protection from vaccine preventable illnesses. Timely preventive care should be prioritized., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Animal-assisted therapy (AAT) is a therapeutic concept, which has only recently been explored in more detail within the palliative care setting. A programme of AAT was begun in June 2014 at the Interdisciplinary Centre for Palliative Medicine of the University Hospital Dusseldorf, Germany. The AAT sessions were performed by two trained and certified dog assistant therapy teams (DATT). To date only very limited scientific data are available with regard to feasibility, therapeutic indications and efficacy of AAT in palliative care. The present qualitative study aims to describe the first year's practice and experience of AAT after implementation as an integral part of adjunctive therapy options offered within an academic palliative care centre., Methods: This study is a qualitative content analysis of all post-encounter protocols of AAT interventions recorded by the dog handlers from June 2014 through May 2015. Qualitative content analysis was conducted according to Mayring's approach; the report followed the recommendations of the Standards for Reporting Qualitative Research (SRQR)., Results: Fifty-two patients received 84 AAT interventions, with only 18 patients receiving more than one intervention due to discharge or death. In 19 cases relatives also participated in the AAT session. The inductive coding process yielded four main categories. One hundred and fifty-three codes related to the content and structure of the AAT sessions, with physical contact with the dog taking considerable precedence. The AAT sessions included conversations with the dog handler, 10.5% of which related to the current health state as well as to discussions around death and dying. Eighty-nine codes related to perceived emotional responses, with pleasure being the most often observed response. Two hundred and seventeen codes related to the effects of the AAT sessions, identifying the dog as a catalyst of communication and observing patients' physical activation or relaxation., Conclusions: AAT may constitute a valuable and practicable adjunct to the interdisciplinary therapeutic repertoire of palliative care in the hospital setting. The results of this study suggest that patients may potentially benefit from AAT in terms of facilitated communication, positive emotional responses, enhanced physical relaxation or motivation for physical activation. These early stage results will need to be followed-up by more robust study designs.

Background: Despite the approved use of live-attenuated intranasal influenza vaccine (LAIV) for seasonal immunization of patients with cystic fibrosis (CF), many questions remain unanswered regarding the timing, duration, and types of adverse events that occur following administration of this vaccine., Methods: In 2012 and 2013, 264 LAIV doses were administered to 198 patients aged 2-19 with CF. Vaccinees were followed prospectively for 55 days after vaccination (day 0) and information on adverse events was collected. Bayesian change-point analysis was used to identify the risk period following LAIV during which participants had a higher risk of reporting adverse events. Multivariable zero-inflated Poisson regression models were then used to estimate the adjusted incidence rate ratio (aIRR) and 95% credible interval (CrI) of reporting each adverse event in the risk period versus the control period., Results: There was a higher risk of reporting serious adverse events (SAEs) (aIRR 1.45, 95% CrI (0.29, 5.17)) and solicited symptoms during days 0-6 of follow-up compared to control period days 7-55. However, most SAEs were not causally related to LAIV and the solicited symptom episodes were brief, usually lasting 1-2 days. There was no increased risk of antibiotic prescriptions for respiratory conditions in the risk vs. control periods (aIRR 0.48, 95% CrI (0.23, 0.91))., Conclusions: Adverse events were most common 0-6 days after LAIV administration but were generally benign and self-limiting. Pulmonary exacerbations did not increase in frequency., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objectives: To describe the criteria that currently guide empiric antibiotic treatment in children admitted to Canadian PICUs., Design: Cross-sectional survey., Setting: Canadian PICUs., Subjects: Pediatric intensivists and pediatric infectious diseases specialists., Interventions: None., Measurements and Main Results: We used focus groups and literature review to design the survey questions and its four clinical scenarios (sepsis, pneumonia, meningitis, and intra-abdominal infections). We analyzed our results using descriptive statistics and multivariate linear regression. Our response rate was 60% for pediatric intensivists (62/103) and 36% for pediatric infectious diseases specialists (37/103). Variables related to patient characteristics, disease severity, pathogens, and clinical, laboratory, and radiologic infection markers were associated with longer courses of antibiotics, with median increment ranging from 1.75 to 7.75 days. The presence of positive viral polymerase chain reaction result was the only variable constantly associated with a reduction in antibiotic use (median decrease from, -3.25 to -8.25 d). Importantly, 67-92% of respondents would still use a full course of antibiotics despite positive viral polymerase chain reaction result and marked clinical improvement for patients with suspected sepsis, pneumonia, and intra-abdominal infection. Clinical experience was associated with shorter courses of antibiotics for meningitis and sepsis (-1.3 d [95% CI, -2.4 to -0.2] and -1.8 d [95% CI, -2.8 to -0.7] per 10 extra years of clinical experience, respectively). Finally, site and specialty also influenced antibiotic practices., Conclusions: Decisions about antibiotic management for PICU patients are complex and involve the assessment of several different variables. With the exception of a positive viral polymerase chain reaction, our findings suggest that physicians rarely consider reducing the duration of antibiotics despite clinical improvement. In contrast, they will prolong the duration when faced with a nonreassuring characteristic. The development of objective and evidence-based criteria to guide antibiotic therapy in critically ill children is crucial to ensure the rational use of these agents in PICUs.

Purpose of Review: Neonates in the neonatal ICU (NICU) are uniquely vulnerable to colonization and infection with pathogens such as multidrug resistant Gram-negative bacteria, which in turn are associated with increased infection-related morbidities and higher case-fatality rates. We reviewed the English, French, and German language literature published between 2015 and 2017, for reports of NICU outbreaks., Recent Findings: A total of 39 outbreaks in NICUs were reported with Gram-negative bacteria (n = 21; 54%) causing most, and extended spectrum beta-lactamase-producing organisms being the most frequent resistance mechanism reported (n = 5). Five viral outbreaks were reported (respiratory syncytial virus = 3). A significant proportion of outbreaks (33%) did not identify a source. Whole genome sequencing was used more (n = 6 reports). The most common described infection prevention and control interventions included staff and parent education on hand hygiene, patient isolation, additional contact precautions, including discontinuation of 'kangaroo care', and cohorting. Reporting and publication bias are likely common., Summary: NICUs must be vigilant in identifying outbreaks, conduct comprehensive investigations, and implement targeted infection prevention and control strategies. Molecular epidemiology capacities are an essential element in outbreak investigation. More studies are needed to determine the added value of active colonization screening and their impact on outbreak development.

OBJECTIVE We examined the impact of methicillin-resistant Staphylococcus aureus (MRSA) guidelines in Québec adult hospitals from January 1, 2006, to March 31, 2015, by examining the incidence rate reduction (IRR) in healthcare-associated MRSA bloodstream infections (HA-MRSA), using central-line associated bloodstream infections (CLABSIs) as a comparator. METHODS In this study, we utilized a quasi-experimental design with Poisson segmented regression to model HA-MRSA and CLABSI incidence for successive 4-week surveillance segments, stratified by teaching status. We used 3 distinct periods with 2 break points (April 1, 2007, and January 3, 2010) corresponding to major MRSA guideline publications and updates. RESULTS Over the study period, HA-MRSA incidence decreased significantly in adult teaching facilities but not in nonteaching facilities. Prior to MRSA guideline publication (2006-2007), HA-MRSA incidence decrease was not significant (P=.89), while CLABSI incidence decreased by 4% per 4-week period (P=.05). After the publication of guidelines (2007-2009), HA-MRSA incidence decreased significantly by 1% (P=.04), while no significant decrease in CLABSI incidence was observed (P=.75). HA-MRSA and CLABSI decreases were both significant at 1% for 2010-2015 (P<.001 and P=.01, respectively). These decreases were gradual rather than sudden; break points were not significant. Teaching facilities drove these decreases. CONCLUSION During the study period, HA-MRSA and CLABSI rates decreased significantly. In 2007-2009, the significant decrease in HA-MRSA rates with stable CLABSI rates suggests an impact from MRSA-specific guidelines. In 2010-2015, significant and equal IRRs for HA-MRSA and CLABSI may be due to the continuing impact of MRSA guidelines, to the impact of new interventions targeting device-associated infections in general by the 2010-2015 Action Plan, or to a combination of factors. Infect Control Hosp Epidemiol 2017;38:840-847.

Background: In children, the 13 and 10-valent pneumoccocal conjugate vaccines (PCV13/10) are currently approved for the prevention of invasive pneumococcal disease (IPD). Acceptability is a key consideration in the implementation of a vaccine program and it is recognized that health professional's attitudes and opinions towards vaccines are independent predictors of the success of an immunization program. We aimed to survey the beliefs and attitudes for the two available PCVs in health care professionals and immunization experts., Findings: We interviewed 21 members of Canadian immunization committees and/or participants working in frontline healthcare delivery. Overall, participants predominantly preferred PCV-13 over PCV10. For most, AOM should not be taken into considerations in decisions for pneumococcal vaccination programs implementation. AOM was considered an important endpoint of the program but an ineffective measure of program success due to the lack of surveillance for the condition. Recent evidence pertaining to PCV10 cross-protection against 19A did not affect preference but had an impact on perceptions regarding pricing., Conclusion: To consider implementing any changes to the current program, most participants would require more evidence regarding PCV10 cross-protection and effectiveness against OM. Decreasing vaccine price was cited as a positive outcome of funding both vaccines., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: The objective of this study was to explore the effects of viral co-detection in individuals recently vaccinated with the live-attenuated intranasal influenza virus vaccine (LAIV) on the detection of influenza RNA., Methods: Before the 2013-2014 influenza season, nasal swabs were obtained from 59 pediatric participants with cystic fibrosis (CF) and 17 of their healthy siblings immediately before vaccination and 4 times during the week of follow-up. Real-time RT-PCR assays were used to detect influenza RNA. Co-detection of a non-influenza respiratory virus (NIRV) at the time of vaccination was determined by a multiplex RT-PCR assay. Differences in the proportions and rates of influenza detection and their 95% credible intervals (CrI) were estimated., Results: Influenza RNA was detected in 16% fewer participants (95% CrI: -7, 39%) throughout follow-up in the NIRV-positive group compared with the NIRV-negative group (59% vs. 75%). This was also observed in participants with CF alone (66% vs. 74%; RD = 8% 95% CrI: -16, 33%) as well as in healthy participants only (75% vs. 30%; RD = 45%, 95% CrI: -2, 81%). Influenza was detected in NIRV-negative subjects for 0.49 d more compared with NIRV-positive subjects (95% CrI: -0.37, 1.26)., Conclusion: The observed proportion of subjects in whom influenza RNA was detected and the duration of detection differed slightly between NIRV- positive and -negative subjects. However, wide credible intervals for the difference preclude definitive conclusions. If true, this observed association may be related to a recent viral respiratory infection, a phenomenon known as viral interference.

Background: The management of paediatric asthma exacerbations is based on trials in children of all ages. Recent studies from 2009 raised the possibility that preschoolers (younger than 6 years) with viral-induced wheezing and children exposed to tobacco smoke might be at an increased risk of treatment failure. The study objective was to identify factors associated with management failure in children presenting to the emergency department with moderate or severe asthma exacerbations., Methods: We undertook a prospective, multicentre cohort study of children aged 1-17 years presenting to five emergency departments with moderate or severe asthma (defined as a Pediatric Respiratory Assessment Measure [PRAM] of 4 to 12). Children received oral corticosteroids and severity-specific inhaled bronchodilator therapy. The primary outcome was emergency department management failure (hospital admission, prolonged emergency department therapy [≥8 h], or relapse within 72 h of discharge from the emergency department with admission to hospital or prolonged emergency department stay). Viral cause was ascertained by PCR on nasopharyngeal specimens and environmental tobacco smoke exposure by salivary cotinine concentration. This study is registered at ClinicalTrials.gov (NCT02013076)., Findings: Between Feb 14, 2011, and Dec 20, 2013, we screened 1893 children and enrolled 1012 eligible children. Of those eligible children, 973 participants were included in the analysis. 165 (17%) of 965 children experienced management failure in the emergency department, which was significantly associated with viral detection (110 [19%] of 579 participants with virus detection vs 46 [13%] of 354 participants without viral detection, odds ratio [OR] 1·57; 95% CI 1·04-2·37), fever (24% vs 15%, 1·96; 1·32-2·92), baseline PRAM (OR 1·38 per 1-point increase; 1·22-1·56), oxygen saturation of less than 92% (50% vs 12%, 3·94; 1·97-7·89), and presence of symptoms between exacerbations (21% vs 16%, 1·73; 1·13-2·64). Age, salivary cotinine concentration, and oral corticosteroids dose were not significantly associated with management failure. Viral detection (67% vs 46%, p<0·0001) and fever (31% vs 16%, p<0·0001) occurred more frequently in preschoolers than in older children. Viral detection was also associated with reduced speed of recovery over the 10 days after discharge., Interpretation: In children presenting with moderate or severe asthma, viral detection, but not age, was associated with failure of symptom management, independently from exacerbation severity (ie, baseline PRAM and oxygen saturation), fever, and symptom chronicity (viral detection). Although it did not reach statistical significance, the association between treatment management failure and exposure to tobacco smoke warrants further investigation., Funding: Canadian Institutes of Health Research., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

OBJECTIVE Central-line-associated bloodstream infections (CLABSI) are an important cause of morbidity and mortality in neonates. We aimed to determine whether intra-abdominal pathologies are an independent risk factor for CLABSI. METHODS We performed a retrospective matched case-control study of infants admitted to the neonatal intensive care units (NICUs) of the Montreal Children's Hospital (Montreal) and the Royal Alexandra Hospital, Edmonton, Canada. CLABSI cases that occurred between April 2009 and March 2014 were identified through local infection control databases. For each case, up to 3 controls were matched (National Healthcare Safety Network [NHSN] birth weight category, chronological age, and central venous catheter (CVC) dwell time at the time of CLABSI onset). Data were analyzed using conditional logistic regression. RESULTS We identified 120 cases and 293 controls. According to a matched univariate analysis, the following variables were significant risk factors for CLABSI: active intra-abdominal pathology (odds ratio [OR], 3.4; 95% confidence interval [CI], 1.8-6.4), abdominal surgery in the prior 7 days (OR, 3.5; 95% CI, 1.0-10.9); male sex (OR, 1.7; 95% CI, 1.1-2.6) and ≥3 heel punctures (OR, 4.0; 95% CI, 1.9-8.3). According to a multivariate matched analysis, intra-abdominal pathology (OR, 5.9; 95% CI, 2.5-14.1), and ≥3 heel punctures (OR, 5.4; 95% CI, 2.4-12.2) remained independent risk factors for CLABSI. CONCLUSION The presence of an active intra-abdominal pathology increased the risk of CLABSI by almost 6-fold. Similar to CLABSI in oncology patients, a subgroup of CLABSI with mucosal barrier injury should be considered for infants in the NICU with active intra-abdominal pathology. Infect Control Hosp Epidemiol 2016;1446-1452.

Background: For patients who have experienced adverse events following immunization (AEFI) or who have specific medical conditions, there is limited evidence regarding the best approach to immunization. The Special Immunization Clinics (SICs) Network was established to standardize patient management and assess outcomes after reimmunization. The study objective was to describe the first 2 years of the network's implementation., Methods: Twelve SICs were established across Canada by infectious diseases specialists and allergists. Inclusion criteria were as follows: local reaction ≥ 10 cm, allergic symptoms < 24 hours postimmunization, neurologic symptoms and other AEFI or medical conditions of concern. Eligible patients underwent a standardized evaluation, causality assessment was performed, immunization recommendations were made by expert physicians and patients were followed up to capture AEFI. After individual consent, data were transferred to a central database for analysis., Results: From June 2013 to May 2015, 151 patients were enrolled. Most were referred for prior AEFI (132/151, 87%): 42 (32%) for allergic-like reactions, 31 (23%) for injection-site reactions, 20 (15%) for neurologic symptoms and 39 (30%) for other systemic symptoms. Nineteen patients (13%) were seen for underlying conditions that complicated immunization. Reimmunization was recommended for 109 patients, 60 of whom (55%) were immunized and followed up. Eleven patients (18%) experienced recurrence of their AEFI; none were serious (eg, resulting in hospitalization, permanent disability or death)., Conclusions: The most frequent reasons for referral to a SIC were allergic-like events and injection site reactions. Reimmunization was safe in most patients. Larger studies are needed to determine outcomes for specific types of AEFI.

Background: Only eight women out of one hundred diagnosed with ovarian epithelial cancers, which progressed to the clinical stage IV, survive 10 years. First line therapies: surgery, chemotherapy, and radiation therapy inflict very serious iatrogenic consequences. Passive immunotherapy of ovarian cancers offers only low efficacy. Prophylactic and therapeutic vaccines for ovarian cancers are not available. Interestingly, prophylactic vaccines for Hepatitis B Viruses (HBV) are very effective., Specific Aim: The specific aim of this work was to design, synthesize, and administer biomolecules, which would engage prophylactic, vaccination-induced immunity for HBV towards killing of ovarian cancer cells with high specificity and efficacy., Patients: Tissue biopsies, ascites, and blood were acquired from the patients, whose identities were entirely concealed in accordance with the Declaration of Helsinki, pursuant to the Institutional Review Board approval, and with the Patients' informed consent., Methods and Results: By biomolecular engineering, we have created a novel family of biomolecules: antibody × vaccine engineered constructs (AVEC: anti-HER-2 × HBsAg). We have collected the blood from the volunteers, and measured the titers of anti-HBV antibodies resulting from the FDA approved and CDC scheduled HBV vaccinations. We have acquired tumor biopsies, ascites, and blood from patients suffering from the advanced ovarian cancers. We have established cultures of HER-2 over-expressing epithelial ovarian cancers: OV-90, TOC-112D, SKOV-3, as well as human ovary surface epithelial (HOSE) and human artery endothelial (HAE) cells. Treatment of the HER-2+ ovarian cancer cells with AVEC: anti-HER-2 × HBsAg, accompanied by administration of blood drawn from patients with high titers of the anti-HBV antibodies, resulted in much higher therapeutic efficacy as compared to treatment with the naked anti-HER-2 antibodies alone and/or with the relevant isotype antibodies. This treatment had practically no effect upon the HOSE and HAE cells., Discussion: Herein, we report attaining the great improvement in eradication efficacy of ovarian epithelial cancer cells' by engaging prophylactic immunity against HBV; thus creating a novel paradigm for immunotherapy of ovarian cancer. We have accomplished that by designing, synthesis, and administration of AVEC. Therefore, the HBV vaccination acquired immunity mounts immune response against the vaccine, but AVEC redirect, accelerate, and amplify this immune response of all the elements of the native and adaptive immune system against ovarian cancer. Our novel paradigm of immunotherapy is currently streamlined to clinical trials also of other cancers, while also engaging prophylactic and acquired immunity., Conclusion: Novel antibody-vaccine engineered constructs (AVEC) create the solid foundation for redirected, accelerated, and amplified prophylactic, HBV vaccination-induced immunity immunotherapy (RAAVIIT) of ovarian cancers.

Objectives: Empirical treatment of uncomplicated urinary tract infections (UTIs) in women should be based on local susceptibility data. We aimed to generate regional and provincial cumulative antibiograms combining data from different laboratory information systems and determine the impact of basic patient characteristics on susceptibility results., Methods: All positive urine samples for Escherichia coli obtained from women aged 18-65 years old in outpatient settings between 1 April 2010 and 31 March 2015 from four hospitals in Quebec, Canada, were included. The cumulative antibiogram for ciprofloxacin, nitrofurantoin and trimethoprim/sulfamethoxazole was calculated. A clinically significant difference in susceptibility profile was defined as factor(s) that lowered the susceptibility proportion below 80%., Results: A total of 36 293 positive urine cultures were analysed. In the last year of the study, the proportion of susceptibility for ciprofloxacin, nitrofurantoin and trimethoprim/sulfamethoxazole was 90.3%, 95.4% and 81.9%, respectively. The susceptibility proportion was <80% for trimethoprim/sulfamethoxazole in the Montreal region (73.4%; 95% CI 71.1%-75.9%), whereas it remained >80% for the other regions. A significant decrease in susceptibility with time was identified for ciprofloxacin (92.1%-90.3%, P < 0.001) and nitrofurantoin (97.1%-95.4%, P < 0.001). Increasing age, recent hospitalization and site of collection were associated with an increase in resistance for certain antibiotics., Conclusions: Overall, all first-line antimicrobials remain acceptable choices for empirical treatment of uncomplicated UTIs in women in Quebec. The regional variability in susceptibility data within a single province emphasizes the importance of local susceptibility data to inform the development of empirical treatment guidelines for UTIs., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Vaccination program evaluation includes assessment of vaccine uptake and direct vaccine effectiveness (VE). Often examined separately, we propose a design to estimate rotavirus vaccination coverage using controls from a rotavirus VE test-negative case-control study and to examine coverage following implementation of the Quebec, Canada, rotavirus vaccination program. We present our assumptions for using these data as a proxy for coverage in the general population, explore effects of diagnostic accuracy on coverage estimates via simulations, and validate estimates with an external source. We found 79.0% (95% confidence interval, 74.3%, 83.0%) ≥2-dose rotavirus coverage among participants eligible for publicly funded vaccination. No differences were detected between study and external coverage estimates. Simulations revealed minimal bias in estimates with high diagnostic sensitivity and specificity. We conclude that controls from a VE case-control study may be a valuable resource of coverage information when reasonable assumptions can be made for estimate generalizability; high rotavirus coverage demonstrates success of the Quebec program., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Context: NICUs in the province of Québec have seen an increase in hVICoNS, detected in the clinical laboratory., Objective: To investigate the clinical relevance of hVICoNS on the course of infection, and to determine the prevalence of hVICoNS sepsis in the NICU., Methods: We searched MEDLINE, EMBASE, and PubMed from 1 January 1980 to 1 July 2016. Both observational and interventional studies were considered eligible if they provided data on hVICoNS in the NICU population. Two investigators independently reviewed studies for data extraction. Data extracted included: number of CoNS cultures, prevalence of hVICoNS, and clonality of strains., Results: Of the 613 studies identified, 19 studies were reviewed, and 5 studies included in the final review. No studies addressed the clinical significance of hVICoNS in the NICU. The prevalence of hVICoNS in the NICU varied greatly, ranging from 2.3% to 100%., Limitations: Publication bias could not be assessed, and risk of bias in some of the included studies due to small sample size and poor methods reporting. The quality of all included studies was low according to GRADE criteria, and the inclusion criteria restricted to either English or French studies., Conclusions: Our review suggests that heteroresistance to vancomycin is much more common than previously believed. Our search however did not identify any studies that explicitly assessed any clinical implications of hVICoNS infections, thereby highlighting the need for research to assess the true impact of hVICoNS infection and to determine its significance on patient mortality and morbidity in the NICU., Competing Interests: The authors have declared that no competing interests exist.

BACKGROUND Following implementation of bundled practices in 2009 in Quebec and Canadian intensive care units (ICUs), we describe CLABSI epidemiology during the last 8 years in the province of Québec (Canada) and compare rates with Canadian and American benchmarks. METHODS CLABSI incidence rates (IRs) and central venous catheter utilization ratios (CVCURs) by year and ICU type were calculated using 2007-2014 data from the Surveillance Provinciale des Infections Nosocomiales (SPIN) program. Using American and Canadian surveillance data, we compared SPIN IRs to rates in other jurisdictions using standardized incidence ratios (SIRs). RESULTS In total, 1,355 lab-confirmed CLABSIs over 911,205 central venous catheter days (CVC days) were recorded. The overall pooled incidence rate (IR) was 1.49 cases per 1,000 CVC days. IRs for adult teaching ICUs, nonteaching ICUs, neonatal ICUs (NICUs), and pediatric ICUs (PICUs) were 1.04, 0.91, 4.20, and 2.15 cases per 1,000 CVC days, respectively. Using fixed SPIN 2007-2009 benchmarks, CLABSI rates had decreased significantly in all ICUs except for PICUs by 2014. Rates declined by 55% in adult teaching ICUs, 52% in adult nonteaching ICUs, and 38% in NICUs. Using dynamic American and Canadian CLABSI rates as benchmarks, SPIN adult teaching ICU rates were significantly lower and adult nonteaching ICUs had lower or comparable rates, whereas NICU and PICU rates were higher. CONCLUSION Québec ICU CLABSI surveillance shows declining CLABSI rates in adult ICUs. The absence of a decrease in CLABSI rate in NICUs and PICUs highlights the need for continued surveillance and analysis of factors contributing to higher rates in these populations. Infect Control Hosp Epidemiol 2016;1-9.

Coagulase-negative staphylococci (CoNS) have become the leading cause of bloodstream infections (BSIs) in intensive care units (ICUs), particularly in premature neonates. Vancomycin-intermediate heteroresistant CoNS (hVICoNS) have been identified as sources of BSIs worldwide, and their potential to emerge as significant pathogens in the neonatal ICU (NICU) remains uncertain. This study describes the molecular epidemiology of an outbreak of vancomycin-heteroresistant (hV) Staphylococcus epidermidis central-line-associated BSI (CLABSI) in a single tertiary care NICU and compares it to a second tertiary care NICU that had not been associated with an outbreak. Between November 2009 and April 2014, 119 S. epidermidis CLABSIs were identified in two tertiary care NICUs in Quebec, Canada. Decreased vancomycin susceptibility was identified in about 88% of all collected strains using Etest methods. However, discrepancies were found according to the Etest and population analysis profiling-area under the concentration-time curve (PAP-AUC) methods used. All strains were susceptible to linezolid, and a few isolates were nonsusceptible to daptomycin. Great genetic diversity was observed within the collection, with 31 pulsed-field gel electrophoresis (PFGE) patterns identified. The outbreak strains were all determined to be heteroresistant to vancomycin and were polyclonal. The study identified two major clones, PFGE patterns E and G, which were found in both NICUs across the 5-year study period. This suggests the persistence of highly successful clones that are well adapted to the hospital environment. hV S. epidermidis seems more common than currently realized in the NICU, and certain hV S. epidermidis clones can become endemic to the NICU. The reservoirs for these clones remain unknown at this time, and identification of the reservoirs is needed to better understand the impact of hV S. epidermidis in the NICU and to inform infection prevention strategies. In addition, there is a need to investigate and validate hV determination protocols for different species of CoNS., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

BACKGROUND Polymerase chain reaction (PCR) assays based on the detection of the toxin B gene are replacing enzyme-linked immunosorbent assay (ELISA)-based toxin production detection or cell cytotoxicity assay in most laboratories. OBJECTIVE To determine the proportion of pediatric patients diagnosed with Clostridium difficile infection by PCR who would have also been diagnosed by ELISA and to compare the clinical characteristics of PCR+/ELISA+ vs PCR+/ELISA- patients. METHODS Using the microbiology laboratory information system, stool samples positive for C. difficile by PCR between October 2010 and July 2014 were identified. Using frozen stool specimens, an ELISA for toxin A and B was performed. A retrospective medical chart review was conducted to obtain demographic and clinical data. Duplicate samples were excluded. RESULTS A total of 136 PCR-positive samples underwent ELISA testing: 54 (40%) were positive for toxin A or B. The mean (SD) age of the entire cohort was 8.5 (6.2) years. There was no difference in age, gender, clinical manifestation, previous medical problems, and management between patients positive or negative by ELISA. However, patients positive by ELISA were more likely to have had a recent exposure to antibiotics (67.9% vs 50%; crude odds ratio, 2.1 [95% CI, 1.03-4.28]). CONCLUSION In our pediatric population, 60% of patients with C. difficile diagnosed by PCR had no toxin detectable by ELISA. ELISA-negative patients were less likely to have received an antibiotic recently compared with ELISA-positive patients. These results highlight the need to standardize laboratory criteria for the diagnosis of C. difficile infections in children. Infect Control Hosp Epidemiol 2016;37:1087-1093.

Ultraviolet (UV)-induced DNA damage is a major risk factor for skin cancers including melanoma. UVRAG, originally identified to complement UV sensitivity in xeroderma pigmentosum (XP), has since been implicated in modulating macroautophagy/autophagy, in coordinating different intracellular trafficking pathways, and in maintaining chromosomal stability. Intriguingly, our recent study has demonstrated that UVRAG plays an essential role in protecting cells from UV-induced DNA damage by activating the nucleotide excision repair (NER) pathway. Since NER is the major mechanism by which cells maintain DNA integrity against UV insult, the inactivation of UVRAG seen in some melanoma may impart these cells with an ability to accumulate high-load UV mutagenesis, leading to cancer progression. Thus, this property of UVRAG has untapped potential to be of fundamental importance in understanding the genetics and pathogenesis of human skin cancer.

Background.  We aimed to explore the detection profile of influenza viruses following live-attenuated intranasal influenza vaccination (LAIV) in children aged 2-19 years with and without cystic fibrosis (CF). Methods.  Before the 2013-2014 influenza season, flocked nasal swabs were obtained before vaccination and 4 times in the week of follow-up from 76 participants (n CF : 57; n healthy : 19). Influenza was detected by reverse transcription polymerase chain reaction (RT-PCR) assays. A Bayesian hierarchical logistic regression model was used to estimate the effect of CF status and age on influenza detection. Results.  Overall, 69% of the study cohort shed influenza RNA during follow-up. The mean duration of RT-PCR detection was 2.09 days (95% credible interval [CrI]: 1.73-2.48). The odds of influenza RNA detection on day 1 following vaccination decreased with age in years (odds ratio [OR]: 0.82 per year; 95% CrI: 0.70-0.95), and subjects with CF had higher odds of influenza RNA detection on day 1 of follow-up (OR: 5.09; 95% CrI: 1.02-29.9). Conclusion.  Despite the small sample size, our results indicate that LAIV vaccine strains are detectable during the week after LAIV, mainly in younger individuals and vaccinees with CF. It remains unclear whether recommendations for avoiding contact with severely immunocompromised patients should differ for these groups.

Background/aims: The novel prostaglandin E (EP) 3 and prostaglandin F (FP) receptor agonist ONO-9054 is effective in lowering intraocular pressure (IOP) in patients with ocular hypertension and open-angle glaucoma when administered once daily. This study compares the effects of morning (AM) versus evening (PM) dosing of ONO-9054 on tolerability and IOP lowering., Methods: This was a single-centre, randomised, double-masked, two-sequence, placebo-controlled crossover study in 12 subjects with bilateral primary open-angle glaucoma or ocular hypertension. Two 14-day crossover regimens were separated by a 2-week washout: ONO-9054 (1 drop to each eye) in the morning (07:00) and vehicle in the evening (19:00) and vice versa. IOP was measured multiple times during select days. Ocular examinations also evaluated safety and tolerability., Results: Mild ocular hyperaemia, reported by six subjects with PM dosing, was the most frequent adverse event. Mild to moderate dryness was also slightly more frequent after PM dosing. Maximum IOP reduction from baseline occurred on day 2 with decreases from baseline of -7.4 mm Hg (-30.8%) for AM dosing and -9.1 mm Hg, (-38.0%) for PM dosing; after 14 days, mean reduction in IOP was -6.8 mm Hg (-28.6%) for AM dosing and -7.5 mm Hg (-31.0%) for PM dosing., Conclusions: PM dosing of ONO-0954 was associated with a slightly increased frequency of mild hyperaemia and mild to moderate dryness. Both dosing schedules provided sustained reduction in IOP., Trial Registration Number: NCT01670266., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: Rotavirus and norovirus are among the leading causes of pediatric gastroenteritis. We examined the relative burden of pediatric gastroenteritis by etiology and compared the clinical severity of rotavirus and norovirus cases after the November 2011 implementation of publicly funded rotavirus vaccination program in Quebec., Methods: Prospective, active surveillance for acute gastroenteritis among children aged 8 weeks to less than 3 years of age was implemented at 3 hospitals. Participant demographics, clinical histories and stools were collected; stools were tested for rotavirus, norovirus and sapovirus. Risk and absolute differences of several clinical severity outcomes were compared by etiology with adjustment for patient age., Results: From February 2012 to May 2014, 734 eligible active surveillance patients were recruited, and stools from 705 (96.0%) were tested and included in study analyses. Of these, 20.4% [95% confidence interval (CI): 16.5-24.3%] were rotavirus positive and 25.5% (95% CI: 21.3-29.8%) were norovirus positive, representing a difference of 5.1% (95% CI: 0.1-10.1%). When stratified by year, rotavirus and norovirus prevalence were similar from June 2012 to May 2013, but rotavirus prevalence was 21.4% (95% CI: 14.3-28.5%) lower than norovirus from June 2013 to May 2014. On average, rotavirus patients were more likely to be febrile, dehydrated, hospitalized and report more diarrheal episodes at the height of illness in comparison with norovirus patients of the same age., Conclusions: Norovirus infections were more prevalent than rotavirus infections among pediatric gastroenteritis cases hospitalized or seeking emergency care. Rotavirus cases were, on average, more clinically severe than norovirus cases among participants of the same age.

Objective: Well-appearing febrile infants with viral illnesses cannot be distinguished from those with occult life-threatening infections. Infants with respiratory viruses are less likely to have serious bacterial infections; however, current risk-stratification criteria predate widespread viral testing and there are limited data to safely inform physician management with this now common diagnostic tool. This study sought to explore the possible impact of respiratory virus testing on clinical decision-making for the management of febrile young infants<6 weeks old., Methods: A scenario-based survey was sent to emergency department (ED) and inpatient physicians at all 16 Canadian tertiary pediatric centers. Participants were asked questions regarding management decisions with and without results of respiratory virus testing., Results: Response rate was 78% (n=330; 190 ED, 140 inpatient). Detection of a respiratory virus reduced admission rates among 3-week-old (83% vs 95%, P<.001) and 5-week-old infants (36% vs 52%, P<.001). Similarly, empirical antibiotic treatment was decreased by detection of a respiratory virus for 3-week-old (65% vs 92%, P<.001) and 5-week-old infants (25% vs 39%, P<.001). Management of 5-week-old infants differed between ED and inpatient physicians, both in the presence and absence of a respiratory virus. There was no consensus among inpatient physicians regarding admission duration for well infants with a detectable respiratory virus and otherwise negative workup., Conclusions: Respiratory virus testing appears to influence clinical decision-making for febrile infants<6 weeks, reducing both rates of admission and antimicrobial treatment. Important work is needed to better understand how to safely incorporate viral testing for the management of this vulnerable patient population., (Copyright © 2016 by the American Academy of Pediatrics.)

Unlabelled: Two pneumococcal vaccines currently exist and have been recommended for the prevention of pneumococcal infection in adults 65 years of age and older: the 23-valent polysaccharide (PPV23) and the conjugate 13-valent (PCV13) vaccine., Objective: To evaluate and summarize the results from all studies reporting on the vaccine effectiveness of PPV23 in preventing invasive pneumococcal disease (IPD) and community-acquired pneumonia (CAP) in individuals over the age of 50., Methods: Systematic database searches were completed in PubMed, Medline, Embase, CINAHL, Web of Science, and Cochrane. Google Scholar and hand searches of seminal articles and past systematic reviews were employed. Studies were included if they independently evaluated the effect of PPV23 on IPD and/or CAP in adults (50+). Data extraction and quality assessment were both completed independently by two researchers. Quality was assessed using the National Advisory Committee on Immunization methodology for quality assessment. All conflicts were resolved by consensus., Results: The vaccine effectiveness for PPV23 in preventing IPD was 50% (95% CI: 21%-69%) for cohort studies and 54% (95% CI: 32%-69%) for case-control studies. The VE estimates for CAP were 4% (95% CI: -26%-26%) for trials, 17% (95% CI: -26%-45%) for cohort studies, and 7% (95% CI: -10%-21%) for case-control studies., Conclusions: The vaccine effectiveness of PPV23 in preventing IPD and all-cause CAP was consistent with past systematic reviews and similar to the estimates that were reported in the CAPiTA trial evaluating the vaccine effectiveness of PCV13. Consistent benefits were also reported across ecological studies and reports of surveillance data for the general population 50 years and older. The results suggests that the current practice of vaccinating the adults 65 years of age and older with PPV23 would have similar benefits to PCV13 in preventing potential cases of all-serotype IPD and all-cause CAP., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Study Design: Systematic review of measurement properties., Background: Many primary studies have examined the measurement properties, such as reliability, validity, and sensitivity to change, of the Lower Extremity Functional Scale (LEFS) in different clinical populations. A systematic review summarizing these properties for the LEFS may provide an important resource., Objective: To locate and synthesize evidence on the measurement properties of the LEFS and to discuss the clinical implications of the evidence., Methods: A literature search was conducted in 4 databases (PubMed, MEDLINE, Embase, and CINAHL), using predefined search terms. Two reviewers performed a critical appraisal of the included studies using a standardized assessment form., Results: A total of 27 studies were included in the review, of which 18 achieved a very good to excellent methodological quality level. The LEFS scores demonstrated excellent test-retest reliability (intraclass correlation coefficients ranging between 0.85 and 0.99) and demonstrated the expected relationships with measures assessing similar constructs (Pearson correlation coefficient values of greater than 0.7). The responsiveness of the LEFS scores was excellent, as suggested by consistently high effect sizes (greater than 0.8) in patients with different lower extremity conditions. Minimal detectable change at the 90% confidence level (MDC90) for the LEFS scores varied between 8.1 and 15.3 across different reassessment intervals in a wide range of patient populations. The pooled estimate of the MDC90 was 6 points and the minimal clinically important difference was 9 points in patients with lower extremity musculoskeletal conditions, which are indicative of true change and clinically meaningful change, respectively., Conclusion: The results of this review support the reliability, validity, and responsiveness of the LEFS scores for assessing functional impairment in a wide array of patient groups with lower extremity musculoskeletal conditions.

Unlabelled: In November 2011, the province of Quebec, Canada implemented a publicly funded rotavirus (RV) vaccination program using the monovalent RV vaccine (RV1). To assess its impact, trends in passive RV laboratory detection and Emergency Department (ED) visits for gastroenteritis (GE) at two pediatric centers were evaluated., Methods: RV tests performed were extracted from the virology laboratory databases and ED visits for GE between July 1, 2006 and June 30, 2013, from the ED databases of The Montreal Children's Hospital (MCH) and Centre Hospitalier Universitaire de Sherbrooke (CHUS). The percent positive RV tests over time and season duration were assessed using 5-week moving averages. We defined season start and end as the first two and the last two consecutive weeks where the percent positive RV tests were ≥ 10%, respectively., Results: Comparing the pre- and post-vaccination program periods, a decrease in the proportion of positive RV tests was seen: 15.9% vs. 5.1% (p<0.001). Pre-vaccination program, RV seasons started between December and February, peaked in March or April and ended in May. In 2011-2012, the season started in March, peaked in April, and ended in May. In 2012-2013, the season lasted 3 weeks in May. ED visits for GE decreased post-introduction of the RV1 program: from 4.8% to 3.4% in 2011-2012, and 4.2% in 2012-13 (p<0.001). In children <2 years of age, ED GE visits decreased from 7.5% to 4.8% in 2011-2012, and 5.2% in 2012-2013 (p<0.001). Admissions for GE also decreased significantly from 0.41% of all ED visits to 0.14% in 2011-2012 and 0.22% in 2012-2013 (p<0.005)., Conclusion: Implementation of a publicly funded RV vaccination program had a major impact on the epidemiology of RV infections in Quebec: RV seasons have started later and been of shorter duration, peak positives were fewer, and ED visits for GE decreased., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Children with underlying medical conditions should receive influenza vaccine (IV) yearly; yet this remains sub-optimal. We aimed to describe our experience with a tertiary-care hospital-based influenza vaccination clinic for this at-risk population., Methods: From October to December 2012, 2013, and 2014, we ran an influenza vaccination clinic at the Montreal Children's Hospital, where children with high-risk conditions come for their follow-up. Both injectable IV (IIV) and live-attenuated IV (LAIV) were offered free of charge to patients and their household contacts. Upon vaccination, parents were asked to fill a pre-piloted questionnaire., Results: We vaccinated a total of 2640 high-risk children and 1912 household members during the three influenza vaccination seasons. In 2012 and 2013, 631 and 630 patients with chronic illnesses were vaccinated, compared to 1379 in 2014. Caregivers preferred LAIV primarily because no needle was involved (49.0%) and because it was perceived as less painful (46.9%). LAIV was administered to 69% (2012), 55% (2013) and 47% (2014) of high-risk children. The main reason for not receiving LAIV was because it was contra-indicated. A small fraction of children previously vaccinated with LAIV who did not present any contraindication to LAIV opted for IIV: 12/101 (11.8%) in 2013 and 16/272 (5.9%) in 2014. In 2014, this was mainly due to a previous negative experience with LAIV (11/16)., Conclusion: Having an influenza vaccination clinic on site at a tertiary care hospital, where children come for their scheduled visits, facilitates yearly influenza vaccination in children with chronic illnesses. LAIV is preferred by caregivers and patients, when not contraindicated., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objective: The optimal way to measure antimicrobial use in hospital populations, as a complement to surveillance of resistance is still unclear. Using respiratory isolates and antimicrobial prescriptions of nine intensive care units (ICUs), this study aimed to identify the indicator of antimicrobial use that predicted prevalence and incidence rates of resistance with the best accuracy., Methods: Retrospective cohort study including all patients admitted to three neonatal (NICU), two pediatric (PICU) and four adult ICUs between April 2006 and March 2010. Ten different resistance/antimicrobial use combinations were studied. After adjustment for ICU type, indicators of antimicrobial use were successively tested in regression models, to predict resistance prevalence and incidence rates, per 4-week time period, per ICU. Binomial regression and Poisson regression were used to model prevalence and incidence rates, respectively. Multiplicative and additive models were tested, as well as no time lag and a one 4-week-period time lag. For each model, the mean absolute error (MAE) in prediction of resistance was computed. The most accurate indicator was compared to other indicators using t-tests., Results: Results for all indicators were equivalent, except for 1/20 scenarios studied. In this scenario, where prevalence of carbapenem-resistant Pseudomonas sp. was predicted with carbapenem use, recommended daily doses per 100 admissions were less accurate than courses per 100 patient-days (p = 0.0006)., Conclusions: A single best indicator to predict antimicrobial resistance might not exist. Feasibility considerations such as ease of computation or potential external comparisons could be decisive in the choice of an indicator for surveillance of healthcare antimicrobial use.

Objective: Indicators of antimicrobial use have been described previously, but few studies have compared their accuracy in prediction of antimicrobial resistance in hospital settings. This study aimed to identify conditions under which significant differences would be observed in the predictive accuracy of indicators in the context of surveillance of intensive care units (ICUs)., Methods: Ten resistance / antimicrobial use combinations were studied. We used simulation to determine if Québec's network of 81 ICUs or the National Healthcare Safety Network (NHSN) of 2952 ICUs are large enough to allow the detection of predetermined differences between the most accurate and 1) the second most accurate indicator, and 2) the least accurate indicator, in more than 80% of simulations. For each indicator, we simulated absolute errors in prediction for each ICU and each 4-week period, for surveillance lasting up to 5 years. Absolute errors were generated following a binomial distribution, using mean absolute errors (MAEs) observed in 9 ICUs as the average proportion; simulated MAEs were compared using t-tests. This was repeated 1000 times per scenario., Results: When comparing the two most accurate indicators, 80% power was reached less often with the Québec network versus the NHSN (0/20 versus 2/20 scenarios, with 5 years of surveillance data), a finding reinforced when comparing the most and least accurate indicators (3/20 versus 20/20 scenarios). When simulating 1 year of data, scenarios reaching an 80% power dropped to 0/20, comparing the two most accurate indicators with the larger network, and to 1/20, comparing the most and least accurate indicators with the smaller network., Conclusion: Most of the time (72%), identifying an indicator of antimicrobial use predicting antimicrobial resistance with a better accuracy was not possible. The choice of an indicator for an eventual surveillance system should rely on criteria other that predictive accuracy.

Background and Objectives: We assessed monovalent rotavirus (RV1) vaccine effectiveness (VE) in a high-income setting with RV1 predominant use, and examined the burden of pediatric rotavirus gastroenteritis following the implementation of an RV1-only vaccination program., Methods: We conducted active rotavirus gastroenteritis surveillance among children 8 weeks to <3 years of age at three hospitals. Participant information and vaccination histories were collected via parent/guardian interview and medical records. Stool specimens were tested for rotavirus; positive specimens were genotyped. The effect of increasing RV1 coverage on rotavirus prevalence was examined as a weekly time series via binomial regression with a log link function, using either categorical season or mean 2-dose rotavirus seasonal vaccine coverage as the exposure variable. As compared with RV1 vaccine formulation, rotavirus genotypes were classified as homotypic, partly-heterotypic, or heterotypic; prevalence of each was compared by season. A test-negative case-control design was used to examine RV1 VE against hospitalization or emergency visits., Results: We enrolled 866 participants in active surveillance; of these, 384 (44.3%) were eligible for VE analyses. After adjustment for season, we detected a 70.1% (95% CI: 21.9%, 88.6%) relative decrease in rotavirus prevalence in the 2013-14 season compared with 2012-13 season. On average, a 1% increase in ≥2-dose rotavirus coverage among children 1 year of age was associated with a 3.8% (95% CI: 1.8%, 5.8%) relative decrease in rotavirus prevalence. Rotavirus homotypic strain prevalence decreased, with 77% (95% CI: 68%, 89%) versus 8% (95% CI: 0%, 36%) prevalence during the 2011-12 and 2013-14 seasons, respectively. Adjusted 2-dose RV1 VE was 91.2% (95% CI: 61.6%, 98.0%)., Conclusions: RV1 vaccine was highly effective to prevent rotavirus hospitalizations and emergency visits among children <3 years of age in a high-income setting with its predominant use. Our estimates were similar to high-income settings with concurrent RV1 and pentavalent vaccine use., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Safety champions are effective in a variety of safety initiatives; however, there are no reports of their role in hospital-acquired infections prevention., Objective: We aimed to describe the association of the presence of a physician safety champion with our urinary catheter device utilization ratios (DUR) in the Pediatric Intensive Care Unit (PICU)., Methods: Our PICU has incidence rates of catheter-associated urinary tract infections (CAUTI) and urinary catheter DUR above the 90th percentile. Using a quasi-experimental design, we compared our DUR when the PICU team was exposed and unexposed (champion's maternity leaves) to a physician safety champion. Hospital acquired infection (HAI) surveillance of all PICU admissions between April 1st 2009 and June 29th 2013 was done prospectively. To ensure stable acuity of the patient population over time, we used the central venous catheter (CVC) DUR as a control., Results: The urinary catheter DUR was 0.44 (95% confidence interval [CI] 0.42-0.45) during the unexposed period versus 0.39 (95%CI 0.38-0.40) during the exposed period, for an absolute difference of 0.05 (95%CI 0.03-0.06; p<0.0001). The overall CVC DUR increased from 0.57 (95%CI 0.55-0.58) during the unexposed period to 0.63 (95%CI 0.61-0.64) during the exposed period, an absolute increase of 0.06 (95%CI 0.04-0.08; p<0.0001). Comparing the exposed and unexposed periods, adjusting for time trend, we observed a 17% decrease in the urinary catheter DUR when the safety champion was present (odds ratio [OR] 0.83; 95%CI 0.77-0.90). The rate of catheter-associated urinary tract infections did not change., Conclusions: The presence of a unit-based safety champion can have a positive impact on urinary catheter DUR in a PICU.

Children with healthcare-associated Clostridium difficile infection were identified. The incidence increased from 3.2/10,000 patient days in 2007 to 5.2/10,000 patient days in 2011 (p < 0.001). Of 169 isolates, the most common North American Pulsed-Field (NAP) types were NAP4 (n = 43; (25.4%), and NAP1 (n = 25;14.8%) while 55 (32.6%) were non-assigned NAP types., (© The Author 2015. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background & Objectives: Preterm infants are at highest risk for severe rotavirus gastroenteritis. While rotavirus vaccination is recommended for age-eligible, clinically stable preterm infants, controversy exists regarding vaccination of these infants during hospitalization. The objectives of this study were to examine tolerance of pentavalent rotavirus vaccination (RV5) among hospitalized infants and nosocomial rotavirus transmission in the neonatal intensive care units (NICU) at two urban hospitals., Methods: A retrospective, medical chart review of patients receiving RV5 vaccine was conducted to examine clinical histories of vaccine recipients. Average risk differences of gastrointestinal complications were estimated between the three days prior and up to four weeks following RV5 vaccination. A generalized linear regression model was used to examine the association between days since RV5 administration and daily feeding totals, using fixed effects to account for individual-level clustering. Rates of nosocomial rotavirus from active surveillance were compared between pre- and post-NICU-based vaccination periods., Results: From July 1, 2011 to March 30, 2013, RV5 vaccination was initiated for 102 NICU patients. No changes in the average risk of gastrointestinal complications or daily feeding among participants overall were detected following RV5 administration. Rates of nosocomial rotavirus were similar during the periods before and after NICU-based vaccination., Conclusions: On average, RV5 appeared to be well tolerated among vaccine recipients, with no increase in nosocomial rotavirus transmission observed following NICU-based rotavirus vaccination. While the benefits of a RV5 NICU-based vaccination program for otherwise eligible preterm infants seem to outweigh the possible risk of vaccine virus transmission, further studies are needed., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Nontuberculous mycobacteria (NTM) are an increasingly recognized cause of chronic suppurative otitis media in children with tympanostomy tubes. Treatment of this condition is difficult and typically requires a combination of systemic antibiotics and surgical debridement. We present the first case of a 2-year-old male with chronic suppurative otitis media due to NTM who failed systemic antibiotic therapy and was successfully managed with topical boric acid powder. This report highlights the challenges involved in treating this infection, and introduces boric acid as a potentially valuable component of therapy., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Administrative claims contain detailed medication, diagnosis, and procedure data, but the lack of clinical outcomes for rheumatoid arthritis (RA) historically has limited their use in comparative effectiveness research. A claims-based algorithm was developed and validated to estimate effectiveness for RA from data for adherence, dosing, and treatment modifications., Objective: To implement the claims-based algorithm in a U.S. managed care database to estimate biologic cost per effectively treated patient., Methods: The cohort included patients with RA aged 18-63 years in the Optum Research Database who initiated biologic treatment between January 2007 and December 2010 and were continuously enrolled 6 months before through 12 months after the first claim for the biologic (the index date). Patients were categorized as effectively treated by the claims-based algorithm if they met all of the following 6 criteria in the 12-month post-index period: (1) a medication possession ratio ≥ 80% for subcutaneous biologics, or at least as many infusions as specified in U.S. labeling for intravenous biologics; (2) no increase in biologic dose; (3) no switch in biologics; (4) no new nonbiologic disease-modifying antirheumatic drug; (5) no new or increased oral glucocorticoid treatment; and (6) no more than 1 glucocorticoid injection. Drug costs (all biologics) and administration costs (intravenous biologics) were obtained from allowed amounts on claims. Biologic cost per effectively treated patient was defined as total 1-year biologic cost divided by the number of patients categorized by the algorithm as effectively treated with that index biologic. Sensitivity analysis was conducted to examine the total health care costs per effectively treated patient during the first year of biologic therapy., Results: A total of 5,474 individuals were included in the analysis. The index biologic was categorized as effective by the algorithm for 28.9% of patients overall, including 30.6% for subcutaneous biologics and 22.1% for intravenous biologics. The index biologic was categorized as effective in the first year for 32.7% of etanercept (794/2,425), 32.3% of golimumab (40/124), 30.2% of abatacept (89/295), 27.7% of adalimumab (514/1,857), and 19.0% of infliximab (147/773) patients. Mean 1-year biologic cost per effectively treated patient, as defined in the algorithm, was lowest for etanercept ($43,935), followed by golimumab ($49,589), adalimumab ($52,752), abatacept ($62,300), and infliximab ($101,402). The rank order in the sensitivity analysis was the same, except for golimumab and etanercept. , Conclusions: Using a claims-based algorithm in a large commercial claims database, etanercept was the most effective and had the lowest biologic cost per effectively treated patient with RA.

Background: Data on health-related quality of life (HRQoL) changes among Americans aged ≥65 following colorectal cancer (CRC) diagnosis and treatment are limited. This study compared HRQoL changes among CRC patients across stages from before to after diagnosis with matched noncancer controls., Methods: This population-based study used the Surveillance, Epidemiology, and End Results Medicare Health Outcomes Survey (MHOS) data set (1998-2007). Medicare Advantage beneficiaries diagnosed with CRC between their baseline and follow-up MHOS (n = 349) were matched to noncancer controls (n = 1745) using propensity scores. Mixed-effects analysis of covariance models estimated changes in HRQoL (measured by the Medical Outcomes Study Short Form-36/Veterans RAND 12-item Survey) and the ability to perform 6 activities of daily living (ADLs) between baseline and follow-up. Logistic regression models estimated odds ratios for ADL impairments and major depressive disorder (MDD) risk., Results: Mean time between CRC diagnosis and follow-up MHOS was 12.3 ± 9.8 months. Compared with controls, CRC patients had significantly lower scores in all physical and mental health domains at follow-up. The greatest decrements were observed in physical health and were largely driven by declines in the 6 months postdiagnosis and in stage III and IV patients. At follow-up, CRC patients had greater overall ADL impairment and difficulty with dressing, eating, and getting in/out of chairs. CRC patients, particularly stage IV patients, had greater odds of being at risk for MDD relative to controls., Conclusions: This study further underscores the adverse effects of CRC on physical health and the need to support older Americans' basic self-care needs, with attention to later-stage patients' increased debility., (© 2014 American Cancer Society.)

Background: Currently, one lifetime booster of a 23-valent pneumococcal polysaccharide vaccine (PPV23) is recommended for those at highest risk of invasive pneumococcal disease (IPD) 3-5 years after initial vaccination. Due to a lack of evidence on multiple revaccinations, recommendations on repeat revaccination do not exist. We aimed to determine the optimal dose and timing of PPV23 booster in high-risk groups., Methods: We searched Google Scholar, Cochrane, EMBASE, Classic EMBASE, and PubMed for articles published in English and French using the MeSH terms pneumococcal infection, invasive pneumococcal disease, pneumonia, pneumo23, pneumovax 23, PPV23, and 23-valent. Articles were included if they examined dosing regimens of PPV23 (i.e., PPV23 priming and boosting) in adult populations, pediatric populations or both. Two authors independently assessed all titles and abstracts. All potentially relevant articles were chosen by consensus and retrieved for full text review. Two authors independently conducted the inclusion assessment., Results: Database searches resulted in a total of 1233 articles. The review by title and abstracts resulted in the exclusion of 1170 articles, 53 articles were fully reviewed, 2 articles were identified using Google Scholar and 12 articles were finally included. The majority of evidence consistently indicated an increase in antibody response following PPV23 revaccination in both adult and pediatric populations. Evidence on multiple revaccinations was limited and mixed. Revaccination with PPV23 was well tolerated., Conclusion: The majority of evidence reviewed supports PPV23 revaccination in both adult and pediatric populations. However, data on multiple booster PPV23 vaccinations in these populations is needed., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Staphylococci are common pathogens in the neonatal period. Increased survival of premature infants leads to prolonged hospital stay with associated risk factors for developing invasive staphylococcal disease. Challenges of diagnosing coagulase-negative staphylococcal infections result in conflicting definitions and inconsistent clinical practice. Resistance to methicillin influences the choice of empirical therapy., (Copyright © 2015 Elsevier Inc. All rights reserved.)

We describe how admissions/discharges/transfers datasets were carefully reviewed for the computation of patient days and admissions used to monitor resistance and antimicrobial use in 9 intensive care units. A visual inspection of datasets and comparisons with other data sources improved accuracy, completeness, and consistency of computations., (Copyright © 2015 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Vaccinations of premature infants are often delayed despite being at an increased risk of contracting vaccine preventable diseases. This article reviews the current knowledge on the immune response to widely used vaccines, on the protection derived from routine immunization and on vaccine safety and tolerability in a population of preterm infants. Available data evaluating the immune response of preterm infants support early immunization without correction for gestational age. For a number of antigens, the antibody response to initial doses of vaccines may be lower than that of term infants, but protective concentrations are often achieved and memory successfully induced. Vaccines are immunogenic, safe and well tolerated in preterm infants. Preterm infants should be vaccinated using the same schedules as those usually recommended for full-term infants, with the exception of the hepatitis B vaccine, where additional doses should be administered in infants receiving the first dose during the first days of life if they weighed less than 2000 g because of a documented reduced immune response.

Unlabelled: Given the burden of illness associated with influenza, vaccination is recommended for individuals at high risk of complications. The live-attenuated influenza vaccine (LAIV) is administered by intranasal spray, thus directly stimulating mucosal immunity. In this review, we aimed to provide evidence for its efficacy and safety in different paediatric populations. We also share the Quebec experience of LAIV use through a publicly funded vaccination program for children with chronic, high-risk conditions., Results: from randomized controlled trials in healthy children and in asthmatics have demonstrated superior efficacy of LAIV over the injectable vaccine (IIV). LAIV is well tolerated: its administration is associated with runny nose and nasal congestion, but not with asthma exacerbations and is well tolerated in children with cystic fibrosis, when compared to IIV. The vaccine is well accepted by children and parents and can easily be part of vaccination clinics in paediatric tertiary care centres targeting children with chronic, high-risk conditions, not leading to immunosuppression., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objective: To satisfy trainees' operative competency requirements while improving feedback validity and timeliness using a mobile Web-based platform., Design: The Southern Illinois University Operative Performance Rating Scale (OPRS) was embedded into a website formatted for mobile devices. From March 2013 to February 2014, faculty members were instructed to complete the OPRS form while providing verbal feedback to the operating resident at the conclusion of each procedure. Submitted data were compiled automatically within a secure Web-based spreadsheet. Conventional end-of-rotation performance (CERP) evaluations filed 2006 to 2013 and OPRS performance scores were compared by year of training using serial and independent-samples t tests. The mean CERP scores and OPRS overall resident operative performance scores were directly compared using a linear regression model. OPRS mobile site analytics were reviewed using a Web-based reporting program., Setting: Large university-based general surgery residency program., Participants: General Surgery faculty used the mobile Web OPRS system to rate resident performance. Residents and the program director reviewed evaluations semiannually., Results: Over the study period, 18 faculty members and 37 residents logged 176 operations using the mobile OPRS system. There were 334 total OPRS website visits. Median time to complete an evaluation was 45 minutes from the end of the operation, and faculty spent an average of 134 seconds on the site to enter 1 assessment. In the 38,506 CERP evaluations reviewed, mean performance scores showed a positive linear trend of 2% change per year of training (p = 0.001). OPRS overall resident operative performance scores showed a significant linear (p = 0.001), quadratic (p = 0.001), and cubic (p = 0.003) trend of change per year of clinical training, reflecting the resident operative experience in our training program. Differences between postgraduate year-1 and postgraduate year-5 overall performance scores were greater with the OPRS (mean = 0.96, CI: 0.55-1.38) than with CERP measures (mean = 0.37, CI: 0.34-0.41). Additionally, there were consistent increases in each of the OPRS subcategories., Conclusions: In contrast to CERPs, the OPRS fully satisfies the Accreditation Council for Graduate Medical Education and American Board of Surgery operative assessment requirements. The mobile Web platform provides a convenient interface, broad accessibility, automatic data compilation, and compatibility with common database and statistical software. Our mobile OPRS system encourages candid feedback dialog and generates a comprehensive review of individual and group-wide operative proficiency in real time., (Copyright © 2014 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)