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Schlapbach L.J.,University of Queensland | Schlapbach L.J.,Materials Childrens Hospital | Schlapbach L.J.,Gold Coast University Hospital | Straney L.,Monash University | And 7 more authors.
The Lancet Infectious Diseases | Year: 2015

Background: Severe infections kill more than 4·5 million children every year. Population-based data for severe infections in children requiring admission to intensive care units (ICUs) are scarce. We assessed changes in incidence and mortality of severe infections in critically ill children in Australia and New Zealand. Methods: We did a retrospective multicentre cohort study of children requiring intensive care in Australia and New Zealand between 2002 and 2013, with data from the Australian and New Zealand Paediatric Intensive Care Registry. We included children younger than 16 years with invasive infection, sepsis, or septic shock. We assessed incidence and mortality in the ICU for 2002-07 versus 2008-13. Findings: During the study period, 97 127 children were admitted to ICUs, 11 574 (11·9%) had severe infections, including 6688 (6·9%) with invasive infections, 2847 (2·9%) with sepsis, and 2039 (2·1%) with septic shock. Age-standardised incidence increased each year by an average of 0·56 cases per 100 000 children (95% CI 0·41-0·71) for invasive infections, 0·09 cases per 100 000 children (0·00-0·17) for sepsis, and 0·08 cases per 100 000 children (0·04-0·12) for septic shock. 260 (3·9%) of 6688 patients with invasive infection died, 159 (5·6%) of 2847 with sepsis died, and 346 (17·0%) of 2039 with septic shock died, compared with 2893 (3·0%) of all paediatric ICU admissions. Children admitted with invasive infections, sepsis, and septic shock accounted for 765 (26·4%) of 2893 paediatric deaths in ICUs. Comparing 2008-13 with 2002-07, risk-adjusted mortality decreased significantly for invasive infections (odds ratio 0·72, 95% CI 0·56-0·94; p=0·016), and for sepsis (0·66, 0·47-0·93; p=0·016), but not significantly for septic shock (0·79, 0·61-1·01; p=0·065). Interpretation: Severe infections remain a major cause of mortality in paediatric ICUs, representing a major public health problem. Future studies should focus on patients with the highest risk of poor outcome, and assess the effectiveness of present sepsis interventions in children. Funding: National Medical Health and Research Council, Australian Resuscitation Outcomes Consortium, Centre of Research Excellence (1029983). © 2015 Elsevier Ltd.


Samuelsson C.,Skåne University Hospital | Samuelsson C.,Halland Hospital | Sjoberg F.,Linköping University | Karlstrom G.,The Care Registry | And 2 more authors.
Critical Care | Year: 2015

Introduction: Preclinical data indicate that oestrogen appears to play a beneficial role in the pathophysiology of and recovery from critical illness. In few previous epidemiologic studies, however, have researchers analysed premenopausal women as a separate group when addressing potential gender differences in critical care outcome. Our aim was to see if women of premenopausal age have a better outcome following critical care and to investigate the association between gender and use of intensive care unit (ICU) resources. Methods: On the basis of our analysis of 127,254 consecutive Simplified Acute Physiology Score III-scored Swedish Intensive Care Registry ICU admissions from 2008 through 2012, we determined the risk-adjusted 30-day mortality, accumulated nurse workload score and ICU length of stay. To investigate associations with sex, we used logistic regression and multivariate analyses on the entire cohort as well as on two subgroups stratified by median age for menopause (up to and including 45 years and older than 45 years) and six selected diagnostic subgroups (sepsis, multiple trauma, chronic obstructive pulmonary disease, acute respiratory distress syndrome, pneumonia and cardiac arrest). Results: There was no sex difference in risk-adjusted mortality for the cohort as a whole, and there was no sex difference in risk-adjusted mortality in the group 45 years of age and younger. For the group of patients older than 45 years of age, we found a reduced risk-adjusted mortality in men admitted for cardiac arrest. For the cohort as a whole, and for those admitted with multiple trauma, male sex was associated with a higher nurse workload score and a longer ICU stay. Conclusions: Using information derived from a large multiple ICU register database, we found that premenopausal female sex was not associated with a survival advantage following intensive care in Sweden. When the data were adjusted for age and severity of illness, we found that men used more ICU resources per admission than women did. © 2015 Samuelsson et al.; licensee BioMed Central.


Moreira L.,University of Barcelona | Balaguer F.,University of Barcelona | Lindor N.,Mayo Medical School | De La Chapelle A.,Ohio State University | And 19 more authors.
JAMA - Journal of the American Medical Association | Year: 2012

Context: Lynch syndrome is the most common form of hereditary colorectal cancer (CRC) and is caused by germline mutations in DNA mismatch repair (MMR) genes. Identification of gene carriers currently relies on germline analysis in patientswith MMR-deficient tumors, but criteria to select individuals in whom tumor MMR testing should be performed are unclear. Objective: To establish a highly sensitive and efficient strategy for the identification of MMR gene mutation carriers among CRC probands. Design, Setting, and Patients: Pooled-data analysis of 4 large cohorts of newly diagnosed CRC probands recruited between 1994 and 2010 (n=10 206) from the Colon Cancer Family Registry, the EPICOLON project, the Ohio State University, and the University of Helsinki examining personal, tumor-related, and family characteristics, as well as microsatellite instability, tumor MMR immunostaining, and germline MMR mutational status data. Main Outcome Measures: Performance characteristics of selected strategies (Bethesda guidelines, Jerusalem recommendations, and those derived from a bivariate/multivariate analysis of variables associated with Lynch syndrome) were compared with tumor MMR testing of all CRC patients (universal screening). Results: Of 10 206 informative, unrelated CRC probands, 312 (3.1%) were MMR gene mutation carriers. In the population-based cohorts (n=3671 probands), the universal screening approach (sensitivity, 100%; 95% CI, 99.3%-100%; specificity, 93.0%; 95% CI, 92.0%-93.7%; diagnostic yield, 2.2%; 95% CI, 1.7%-2.7%) was superior to the use of Bethesda guidelines (sensitivity, 87.8%; 95% CI, 78.9%-93.2%; specificity, 97.5%; 95% CI, 96.9%-98.0%; diagnostic yield, 2.0%; 95% CI, 1.5%-2.4%; P < .001), Jerusalem recommendations (sensitivity, 85.4%; 95% CI, 77.1%-93.6%; specificity, 96.7%; 95% CI, 96.0%-97.2%; diagnostic yield, 1.9%; 95% CI, 1.4%-2.3%; P < .001), and a selective strategy based on tumor MMR testing of cases with CRC diagnosed at age 70 years or younger and in older patients fulfilling the Bethesda guidelines (sensitivity, 95.1%; 95% CI, 89.8%-99.0%; specificity, 95.5%; 95% CI, 94.7%-96.1%; diagnostic yield, 2.1%; 95% CI, 1.6%-2.6%; P < .001). This selective strategy missed 4.9% of Lynch syndrome cases but resulted in 34.8% fewer cases requiring tumor MMR testing and 28.6% fewer cases undergoing germline mutational analysis than the universal approach. Conclusion: Universal tumor MMR testing among CRC probands had a greater sensitivity for the identification of Lynch syndrome compared with multiple alternative strategies, although the increase in the diagnostic yield was modest. ©2012 American Medical Association. All rights reserved.


Van De Velde N.,University of Quebec at Rimouski | Van De Velde N.,Laval University | Boily M.-C.,University of Quebec at Rimouski | Boily M.-C.,Imperial College London | And 16 more authors.
Journal of the National Cancer Institute | Year: 2012

Background Bivalent and quadrivalent human papillomavirus (HPV) vaccines are now licensed in several countries. Furthermore, clinical trials examining the efficacy of a nonavalent vaccine are underway. We aimed to compare the potential population-level effectiveness of the bivalent, quadrivalent, and candidate nonavalent HPV vaccines.MethodsWe developed an individual-based, transmission-dynamic model of HPV infection and disease in a population stratified by age, gender, sexual activity, and screening behavior. The model was calibrated to highly stratified sexual behavior, HPV epidemiology, and cervical screening data from Canada.ResultsUnder base case assumptions, vaccinating 12-year-old girls (70% coverage) with the bivalent (quadrivalent) vaccine is predicted to reduce the cumulative incidence of anogenital warts (AGWs) by 0.0% (72.1%), diagnosed cervical intraepithelial neoplasia lesions 2 and 3 (CIN2 and -3) by 51.0% (46.1%), and cervical squamous cell carcinoma (SCC) by 31.9% (30.5%), over 70 years. Changing from a bivalent (quadrivalent) to a nonavalent vaccine is predicted to reduce the cumulative number of AGW episodes by an additional 66.7% (0.0%), CIN2 and -3 episodes by an additional 9.3% (12.5%), and SCC cases by an additional 4.8% (6.6%) over 70 years. Differences in predicted population-level effectiveness between the vaccines were most sensitive to duration of protection and the time horizon of analysis. The vaccines produced similar effectiveness at preventing noncervical HPV-related cancers.ConclusionsThe bivalent vaccine is expected to be slightly more effective at preventing CIN2 and -3 and SCC in the longer term, whereas the quadrivalent vaccine is expected to substantially reduce AGW cases shortly after the start of vaccination programs. Switching to a nonavalent vaccine has the potential to further reduce precancerous lesions and cervical cancer. © 2012 The Author.


Nowatzki J.,The Care Registry | Moller B.,Cancer Registry of Norway | Demers A.,The Care Registry | Demers A.,University of Manitoba
Chronic Diseases in Canada | Year: 2011

Introduction: Projecting the burden of cancer is important for evaluating prevention strategies and for administrative planning at cancer facilities. Methods: We projected cancer incidence and counts for the population of Manitoba using population projections from the Manitoba Bureau of Statistics for the years 2006 to 2025 and cancer incidence data from the Manitoba Cancer Registry for the years 1976 to 2005. Data were analyzed using a version of the age-period-cohort model with recommended modifications that was developed and tested in the Nordic countries. Results: The overall incidence of cancer in Manitoba is not projected to change substantially from 2006 to 2025. However, the age-standardized incidence for lung cancer is expected to decrease, particularly for males, highlighting the importance of tobacco prevention. The total number of new cancer cases per year is expected to increase 36% over the projection period, attributable primarily to demographic changes. Conclusion: As the population of Manitoba increases, resource and infrastructure planning will need to account for the expected increase in cancer cases.


Liu H.-W.,University of Calgary | Khan R.,University of Calgary | D'Ambrosi R.,University of Calgary | Krobutschek K.,University of Calgary | And 2 more authors.
Radiotherapy and Oncology | Year: 2013

Purpose: To investigate the influence of tumor and patient characteristics on the target volume obtained from cone beam CT (CBCT) in lung stereotactic body radiation therapy (SBRT). Materials and methods: For a given cohort of 71 patients, the internal target volume (ITV) in CBCT obtained from four different datasets was compared with a reference ITV drawn on a four-dimensional CT (4DCT). The significance of the tumor size, location, relative target motion (RM) and patient's body mass index (BMI) and gender on the adequacy of ITV obtained from CBCT was determined. Results: The median ITV-CBCT was found to be smaller than the ITV-4DCT by 11.8% (range: -49.8 to +24.3%, P < 0.001). Small tumors located in the lower lung were found to have a larger RM than large tumors in the upper lung. Tumors located near the central lung had high CT background which reduced the target contrast near the edges. Tumor location close to center vs. periphery was the only significant factor (P = 0.046) causing underestimation of ITV in CBCT, rather than RM (P = 0.323) and other factors. Conclusions: The current clinical study has identified that the location of tumor is a major source of discrepancy between ITV-CBCT and ITV-4DCT for lung SBRT. © 2013 Elsevier Ireland Ltd. All rights reserved.


Straney L.,The Care Registry
Pediatric Critical Care Medicine | Year: 2016

OBJECTIVES:: Despite World Health Organization endorsed immunization schedules, Bordetella pertussis continues to cause severe infections, predominantly in infants. There is a lack of data on the frequency and outcome of severe pertussis infections in infants requiring ICU admission. We aimed to describe admission rates, severity, mortality, and costs of pertussis infections in critically ill infants. DESIGN:: Binational observational multicenter study. SETTING:: Ten PICUs and 19 general ICUs in Australia and New Zealand contributing to the Australian and New Zealand Paediatric Intensive Care Registry. PATIENTS:: Infants below 1 year of age, requiring intensive care due to pertussis infection in Australia and New Zealand between 2002 and 2014. MEASUREMENTS AND MAIN RESULTS:: During the study period, 416 of 42,958 (1.0%) infants admitted to the ICU were diagnosed with pertussis. The estimated population-based ICU admission rate due to pertussis ranged from 2.1/100,000 infants to 18.6/100,000 infants. Admission rates were the highest among infants less than 60 days old (p < 0.0001). Two hundred six infants (49.5%) required mechanical ventilation, including 20 (4.8%) treated with high-frequency oscillatory ventilation, 16 (3.8%) with inhaled nitric oxide, and 7 (1.7%) with extracorporeal membrane oxygenation. Twenty of the 416 children (4.8%) died. The need for mechanical ventilation, high-frequency oscillatory ventilation, nitric oxide, and extracorporeal membrane oxygenation were significantly associated with mortality (p < 0.01). Direct severe pertussis–related hospitalization costs were in excess of USD$1,000,000 per year. CONCLUSIONS:: Pertussis continues to cause significant morbidity and mortality in infants, in particular during the first months of life. Improved strategies are required to reduce the significant healthcare costs and disease burden of this vaccine-preventable disease. ©2016The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies


Most cases of the 2009 influenza A (H1N1) infection are self-limited, but occasionally the disease evolves to a severe condition needing hospitalization. Here we describe the evolution of the respiratory compromise, ventilatory management and laboratory variables of patients with diffuse viral pneumonitis caused by pandemic 2009 influenza A (H1N1) admitted to the ICU. This was a multicenter, prospective inception cohort study including adult patients with acute respiratory failure requiring mechanical ventilation (MV) admitted to 20 ICUs in Argentina between June and September of 2009 during the influenza A (H1N1) pandemic. In a standard case-report form, we collected epidemiological characteristics, results of real-time reverse-transcriptase--polymerase-chain-reaction viral diagnostic tests, oxygenation variables, acid-base status, respiratory mechanics, ventilation management and laboratory tests. Variables were recorded on ICU admission and at days 3, 7 and 10. During the study period 178 patients with diffuse viral pneumonitis requiring MV were admitted. They were 44 ± 15 years of age, with Acute Physiology And Chronic Health Evaluation II (APACHE II) scores of 18 ± 7, and most frequent comorbidities were obesity (26%), previous respiratory disease (24%) and immunosuppression (16%). Non-invasive ventilation (NIV) was applied in 49 (28%) patients on admission, but 94% were later intubated.Acute respiratory distress syndrome (ARDS) was present throughout the entire ICU stay in the whole group (mean PaO2/FIO2 170 ± 25). Tidal-volumes used were 7.8 to 8.1 ml/kg (ideal body weight), plateau pressures always remained < 30 cmH2O, without differences between survivors and non-survivors; and mean positive end-expiratory pressure (PEEP) levels used were between 8 to 12 cm H2O. Rescue therapies, like recruitment maneuvers (8 to 35%), prone positioning (12 to 24%) and tracheal gas insufflation (3%) were frequently applied. At all time points, pH, platelet count, lactate dehydrogenase assay (LDH) and Sequential Organ Failure Assessment (SOFA) differed significantly between survivors and non-survivors. Lack of recovery of platelet count and persistence of leukocytosis were characteristic of non-survivors. Mortality was high (46%); and length of MV was 10 (6 to 17) days. These patients had severe, hypoxemic respiratory failure compatible with ARDS that persisted over time, frequently requiring rescue therapies to support oxygenation. NIV use is not warranted, given its high failure rate. Death and evolution to prolonged mechanical ventilation were common outcomes. Persistence of thrombocytopenia, acidosis and leukocytosis, and high LDH levels found in non-survivors during the course of the disease might be novel prognostic findings.

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