The objective of this study was to assess potential biases that may influence the validity of contemporary antimicrobial-resistant (AMR) pathogen surveillance systems. Although surveillance data have been widely published and used by researchers and decision makers, little attention has been devoted to the assessment of their validity. A Medline search was used to identify reports, in 2008, of laboratory-based AMR surveillance systems. Identified surveillance systems were appraised for six different types of bias. Scores were assigned as ‘2’ (good), ‘1’ (fair) and ‘0’ (poor) for each bias. The results of this assessment indicate that there are several potential biases that can influence the validity of AMR surveillance information and, therefore, the potential for bias should be considered in the interpretation and use of AMR surveillance data.

BACKGROUND:

The validity of surveillance systems has rarely been a topic of investigation.

OBJECTIVE:

To assess potential biases that may influence the validity of contemporary antimicrobial-resistant (AMR) pathogen surveillance systems.

METHODS:

In 2008, reports of laboratory-based AMR surveillance systems were identified by searching Medline. Surveillance systems were appraised for six different types of bias. Scores were assigned as ‘2’ (good), ‘1’ (fair) and ‘0’ (poor) for each bias.

RESULTS:

A total of 22 surveillance systems were included. All studies used appropriate denominator data and case definitions (score of 2). Most (n=18) studies adequately protected against case ascertainment bias (score = 2), with three studies and one study scoring 1 and 0, respectively. Only four studies were deemed to be free of significant sampling bias (score = 2), with 17 studies classified as fair, and one as poor. Eight studies had explicitly removed duplicates (score = 2). Seven studies removed duplicates, but lacked adequate definitions (score = 1). Seven studies did not report duplicate removal (score = 0). Eighteen of the studies were considered to have good laboratory methodology, three had some concerns (score = 1), and one was considered to be poor (score = 0).

CONCLUSION:

Contemporary AMR surveillance systems commonly have methodological limitations with respect to sampling and multiple counting and, to a lesser degree, case ascertainment and laboratory practices. The potential for bias should be considered in the interpretation of surveillance data.

BACKGROUND:

Although Staphylococcus aureus is a major cause of bloodstream infections, population-based data on these infections in children are limited.

OBJECTIVE:

To describe the epidemiology of S aureus bacteremia in children.

METHODS:

Population-based surveillance for all incident S aureus bacteremias was conducted among children (18 years of age or younger) living in the Calgary Health Region (Alberta) from 2000 to 2006.

RESULTS:

During the seven-year study, 120 S aureus bloodstream infections occurred among 119 patients; 27% were nosocomial, 18% health care associated and 56% community acquired. The annual incidence was 6.5/100,000 population and 0.094/1000 live births. A total of 52% had a significant underlying condition, and this was higher for nosocomial cases. Bone and joint (40%), bacteremia without a focus (33%), and skin and soft tissue infections (15%) were the most common clinical syndromes. Infections due to methicillin-resistant S aureus were uncommon (occurring in one infection) and three patients (2.5%) died.

CONCLUSIONS:

S aureus bacteremia is an important cause of morbidity in the paediatric age group. Underlying medical conditions and implanted devices are important risk factors. Methicillin-resistant S aureus and mortality rates are low.

Background

Case-control studies are a common and efficient means of studying rare diseases or illnesses with long latency periods. Matching of cases and controls is frequently employed to control the effects of known potential confounding variables. The analysis of matched data requires specific statistical methods.

Methods

The objective of this study was to determine the proportion of published, peer-reviewed matched case-control studies that used statistical methods appropriate for matched data. Using a comprehensive set of search criteria we identified 37 matched case-control studies for detailed analysis.

Results

Among these 37 articles, only 16 studies were analyzed with proper statistical techniques (43%). Studies that were properly analyzed were more likely to have included case patients with cancer and cardiovascular disease compared to those that did not use proper statistics (10/16 or 63%, versus 5/21 or 24%, P = 0.02). They were also more likely to have matched multiple controls for each case (14/16 or 88%, versus 13/21 or 62%, P = 0.08). In addition, studies with properly analyzed data were more likely to have been published in a journal with an impact factor listed in the top 100 according to the Journal Citation Reports index (12/16 or 69%, versus 1/21 or 5%, P ≤ 0.0001).

Conclusion

The findings of this study raise concern that the majority of matched case-control studies report results that are derived from improper statistical analyses. This may lead to errors in estimating the relationship between a disease and exposure, as well as the incorrect adaptation of emerging medical literature.

Background

Bloodstream infections (BSI) have been traditionally classified as either community acquired (CA) or hospital acquired (HA) in origin. However, a third category of healthcare-associated (HCA) community onset disease has been increasingly recognized. The objective of this study was to compare and contrast characteristics of HCA-BSI with CA-BSI and HA-BSI.

Methods

All first episodes of BSI occurring among adults admitted to hospitals in a large health region in Canada during 2000-2007 were identified from regional databases. Cases were classified using a series of validated algorithms into one of HA-BSI, HCA-BSI, or CA-BSI and compared on a number of epidemiologic, microbiologic, and outcome characteristics.

Results

A total of 7,712 patients were included; 2,132 (28%) had HA-BSI, 2,492 (32%) HCA-BSI, and 3,088 (40%) had CA-BSI. Patients with CA-BSI were significantly younger and less likely to have co-morbid medical illnesses than patients with HCA-BSI or HA-BSI (p < 0.001). The proportion of cases in males was higher for HA-BSI (60%; p < 0.001 vs. others) as compared to HCA-BSI or CA-BSI (52% and 54%; p = 0.13). The proportion of cases that had a poly-microbial etiology was significantly lower for CA-BSI (5.5%; p < 0.001) compared to both HA and HCA (8.6 vs. 8.3%). The median length of stay following BSI diagnosis 15 days for HA, 9 days for HCA, and 8 days for CA (p < 0.001). Overall the most common species causing bloodstream infection were Escherichia coli, Staphylococcus aureus, and Streptococcus pneumoniae. The distribution and relative rank of importance of these species varied according to classification of acquisition. Twenty eight day all cause case-fatality rates were 26%, 19%, and 10% for HA-BSI, HCA-BSI, and CA-BSI, respectively (p < 0.001).

Conclusion

Healthcare-associated community onset infections are distinctly different from CA and HA infections based on a number of epidemiologic, microbiologic, and outcome characteristics. This study adds further support for the classification of community onset BSI into separate CA and HCA categories.

Background

Fever is one of the most commonly observed abnormal signs in patients with critical illness. However, there is a paucity of evidence to guide the management of febrile patients without acute brain injury and little is known about the biologic response to treatment of fever. As such, observational studies suggest that the treatment of fever is inconsistent. This pilot clinical trial will assess the safety and feasibility of treating febrile critically ill adult patients with an aggressive versus a permissive temperature control strategy. The biologic response to these two different temperature control strategies will also be assessed through analysis of a panel of inflammatory mediators.

Findings

The study population will include febrile adult patients admitted to one of two general medical-surgical intensive care units (ICUs) in Calgary, Alberta, Canada. Patients will be randomized to either an aggressive or permissive fever treatment strategy. The aggressive group will receive acetaminophen 650 mg enterally every 6 hours upon reaching a temperature ≥ 38.3°C and external cooling will be initiated for temperatures ≥ 39.5°C, whereas the permissive group will receive acetaminophen 650 mg every 6 hours upon reaching a temperature ≥ 40.0°C and external cooling for temperatures ≥ 40.5°C. The study will take place over 12 months with the goal of enrolling 120 patients. The primary outcome will be 28-day mortality after study enrolment, with secondary outcomes that will include markers of feasibility (e.g. the enrolment rate, and the number of protocol violations), and levels of select inflammatory and anti-inflammatory mediators.

Discussion

Results from this study will lead to a better understanding of the inflammatory effects of anti-pyretic therapy and will evaluate the feasibility of a future clinical trial to establish the best treatment of fever observed in nearly one half of patients admitted to adult ICUs.

Trial Registration

ClinicalTrials.gov: NCT01173367

Background

Although the association between mortality and admission to intensive care units (ICU) in the "after hours" (weekends and nights) has been the topic of extensive investigation, the timing of discharge from ICU and outcome has been less well investigated. The objective of this study was to assess effect of timing of admission to and discharge from ICUs and subsequent risk for death.

Methods

Adults (≥18 years) admitted to French ICUs participating in Outcomerea between January 2006 and November 2010 were included.

Results

Among the 7,380 patients included, 61% (4,481) were male, the median age was 62 (IQR, 49-75) years, and the median SAPS II score was 40 (IQR, 28-56). Admissions to ICU occurred during weekends (Saturday and Sunday) in 1,708 (23%) cases, during the night (18:00-07:59) in 3,855 (52%), and on nights and/or weekends in 4,659 (63%) cases. Among 5,992 survivors to ICU discharge, 903 (15%) were discharged on weekends, 659 (11%) at night, and 1,434 (24%) on nights and/or weekends. After controlling for a number of co-variates using logistic regression analysis, admission during the after hours was not associated with an increased risk for death. However, patients discharged from ICU on nights were at higher adjusted risk (odds ratio, 1.54; 95% confidence interval, 1.12-2.11) for death.

Conclusions

In this study, ICU discharge at night but not admission was associated with a significant increased risk for death. Further studies are needed to examine whether minimizing night time discharges from ICU may improve outcome.

Vaccination is one of the greatest achievements in public health of the 20th century. However, the success of vaccine uptake and adherence to immunization guidelines seen in pediatric populations has not been observed among adult Canadians. As a result of the disparity in susceptibility to vaccine-preventable disease, there has been an increasing shift of vaccine-preventable childhood diseases into adult populations. Accordingly, morbidity and mortality due to vaccine-preventable illnesses now occur disproportionately in adults. All Canadians, irrespective of age, should have immunity to measles, mumps, rubella, tetanus, diphtheria, pertussis and varicella. All adult Canadians with significant medical comorbidities or those older than 65 years of age should receive the pneumococcal polysaccharide vaccine and yearly trivalent inactivate influenza vaccines. The present review summarizes the burden of illness of these vaccine-preventable diseases in the Canadian adult population and reviews the current immunization recommendations. Vaccination of all Canadians to these common agents remains a vital tool to decrease individual morbidity and mortality and reduce the overall burden of preventable disease in Canada.

Background

Considering that injuries to the gallbladder are rare, the purpose of this study was to evaluate injury patterns, operative procedures and outcomes in patients with trauma to the gallbladder. A retrospective review of traumatic injuries to the gallbladder at an urban level 1 trauma center from 1996 to 2008 was performed. Injuries were identified via imaging or during operative exploration.

Results

Injuries to the gallbladder occurred in 45 patients, 40 (89%) of whom suffered penetrating trauma. Associated injuries were present in 44 (98%) patients, including 10 (22%) pancreatic injuries requiring repair and/or drainage. Patients were severely injured (49% hemodynamically unstable at presentation; mean Injury Severity Score = 20; mean length of stay = 22 days; mortality rate = 24%). Cholecystectomy was performed in 42 patients (93%), while the remaining 3 had drainage only as part of a "damage control" operation related to their critical physiologic status. Injuries to the extrahepatic biliary ducts occurred in 3 patients (7%) as well. Although all patients developed trauma related complications, none were a direct result of their biliary tract injuries.

Conclusion

Injuries to the gallbladder are rare even in the busiest urban trauma centers. Almost all patients have associated intra-abdominal injuries, and nearly 50% of patients are hemodynamically unstable on admission. Rapid cholecystectomy is the treatment of choice for all mechanisms of injury, except when the first operative procedure is of the damage control type.

Background

Salmonella enterica is an important emerging cause of invasive infections worldwide. However, population-based data are limited. The objective of this study was to define the occurrence of S. enterica bacteremia in a large international population and to evaluate temporal and regional differences.

Methods

We conducted population-based laboratory surveillance for all salmonella bacteremias in six regions (annual population at risk 7.7 million residents) in Finland, Australia, Denmark, and Canada during 2000-2007.

Results

A total of 622 cases were identified for an annual incidence of 1.02 per 100,000 population. The incidence of typhoidal (serotypes Typhi and Paratyphi) and non-typhoidal (other serotypes) disease was 0.21 and 0.81 per 100,000/year. There was major regional and moderate seasonal and year to year variability with an increased incidence observed in the latter years of the study related principally to increasing rates of non-typhoidal salmonella bacteremias. Advancing age and male gender were significant risk factors for acquiring non-typhoidal salmonella bacteremia. In contrast, typhoidal salmonella bacteremia showed a decreasing incidence with advancing age and no gender-related excess risk.

Conclusions

Salmonella enterica is an important emerging pathogen and regional determinants of risk merits further investigation.

A study was designed to characterize extended-spectrum-β-lactamase (ESBL)-producing Escherichia coli isolates causing bacteremia over an 8-year period (2000 to 2007) in a large well-defined geographical region. Molecular characterization was done by using isoelectric focusing; PCR; and sequencing of the blaCTX-M-, blaTEM-, blaOXA-, blaSHV-, and plasmid-mediated quinolone resistance determinants. Genetic relatedness was determined by pulsed-field electrophoresis with XbaI and multilocus sequence typing. A total of 67 patients with incident bloodstream infections were identified, and the majority presented with community-acquired infections involving the urinary and biliary tracts. Of the 67 ESBL-producing E. coli isolates recovered, 60 (90%) were positive for blaCTX-M genes; 32 (48%) produced CTX-M-15, 25 (37%) produced CTX-M-14, 1 (2%) produced CTX-M-24, 1 (2%) produced CTX-M-2, and 1 (2%) produced CTX-M-3, while 2 (3%) produced TEM-52 and 5 (7%) produced SHV-2. Twenty-four (36%) isolates were positive for aac(6′)-Ib-cr. The majority of isolates were resistant to ciprofloxacin (60 [90%] isolates) and gentamicin (40 [60%] isolates). The occurrence of ESBL-producing isolates was stable during the first 5 years, but there was a substantial increase from 2005 to 2007, mostly due to clone ST131, which produces CTX-M-15 and CTX-M-14, in blood cultures submitted from the community. Our results illustrated that E. coli clone ST131, which coproduces CTX-M-15, OXA-1, TEM-1, and aac(6′)-Ib-cr, has emerged as an important cause of community-onset bacteremia caused by ESBL-producing E. coli isolates; and this is the first study to identify CTX-M-14 in E. coli clone ST131.

Extended-spectrum-β-lactamase (ESBL)-producing Escherichia coli has recently emerged as a major risk factor for community-acquired, travel-related infections in the Calgary Health Region. Molecular characterization was done on isolates associated with infections in returning travelers using isoelectric focusing, PCR, and sequencing for blaCTX-Ms, blaTEMs, blaSHVs, blaOXAs, and plasmid-mediated quinolone resistance determinants. Genetic relatedness was determined with pulsed-field gel electrophoresis using XbaI and multilocus sequence typing (MLST). A total of 105 residents were identified; 6/105 (6%) presented with hospital-acquired infections, 9/105 (9%) with health care-associated community-onset infections, and 90/105 (86%) with community-acquired infections. Seventy-seven of 105 (73%) of the ESBL-producing E. coli isolates were positive for blaCTX-M genes; 55 (58%) produced CTX-M-15, 13 (14%) CTX-M-14, six (6%) CTX-M-24, one (1%) CTX-M-2, one (1%) CTX-M-3, and one (1%) CTX-M-27, while 10 (10%) produced TEM-52, three (3%) TEM-26, 11 (11%) SHV-2, and four (4%) produced SHV-12. Thirty-one (30%) of the ESBL-producing E. coli isolates were positive for aac(6′)-Ib-cr, and one (1%) was positive for qnrS. The majority of the ESBL-producing isolates (n = 95 [90%]) were recovered from urine samples, and 83 (87%) were resistant to ciprofloxacin. The isolation of CTX-M-15 producers belonging to clone ST131 was associated with travel to the Indian subcontinent (India, Pakistan), Africa, the Middle East, and Europe, while clonally unrelated strains of CTX-M-14 and -24 were associated with travel to Asia. Our study suggested that clone ST131 coproducing CTX-M-15, OXA-1, TEM-1, and AAC(6′)-Ib-cr and clonally unrelated CTX-M-14 producers have emerged as important causes of community-acquired, travel-related infections.

Background

Patient care may be inconsistent during off hours. We sought to determine whether victims of major trauma admitted to hospital on evenings, nights, and weekends suffer increased mortality rates. All victims of major trauma admitted to all four major acute care hospitals in the Calgary Health Region between April 1, 2002 and March 31, 2006 were included. Clinical and outcome information was obtained from regional databases. Weekends were defined as anytime Saturday or Sunday, evenings as 18:00–22:59, and nights as 23:00–07:59.

Results

Four thousand patients were included; 2,901 (73%) were male, the median age was 39.5 [inter-quartile range (IQR), 22.4–58.2] years, and the median injury severity score (ISS) was 20 (IQR, 16–26). Thirty-five percent (1,405) of patients were admitted on a weekend, 30% (1,197) during evenings, and 36% (1,422) at night. Seventy-eight percent (3,106) of cases presented during the "after hours" (evenings, nights, and/or weekends). The in-hospital case-fatality rate was 447 (11%), and was not significantly different during daytime (165/1,381; 37%), evening (128/1,197; 30%), and night (154/1,422; 36%) admissions (p = 0.53), or among patients admitted on weekends as compared to weekdays (157/1,405; 11% vs. 290/2,595; 11%; p = 1.0). Admission during the after hours as compared to business hours (343/3,106; 11% vs. 104/894; 12%; p = 0.63) did not increased risk. A multivariable logistic regression model was developed to assess factors associated with in-hospital death (n = 3,891). Neither admission on weekends nor on evenings or nights increased the risk for in-hospital mortality.

Conclusion

In our region, the time of admission during the day or day of the week does not influence the risk for adverse outcome and may reflect our highly developed multi-hospital acute care and trauma system.

Background

Bloodstream infections are frequent causes of human illness and cause major morbidity and death. In order to best define the epidemiology of these infections and to track changes in occurrence, adverse outcome, and resistance rates over time, population based methodologies are optimal. However, few population-based surveillance systems exist worldwide, and because of differences in methodology inter-regional comparisons are limited. In this report we describe the rationale and propose first practical steps for developing an international collaborative approach to the epidemiologic study and surveillance for bacteremia.

Findings

The founding collaborative participants represent six regions in four countries in three continents with a combined annual surveillance population of more than 8 million residents.

Conclusion

Future studies from this collaborative should lead to a better understanding of the epidemiology of bloodstream infections.

Introduction

Hyperlactatemia is frequent in critically ill patients and is often used as a marker of adverse outcome. However, studies to date have focused on selected intensive care unit (ICU) populations. We sought to determine the occurrence and relation of hyperlactatemia with ICU mortality in all patients admitted to four ICUs in a large regional critical care system.

Methods

All adults ([greater than or equal to] 18 years) admitted to ICUs in the Calgary Health Region (population 1.2 million) during 2003 to 2006 were included retrospectively. Lactate determinations were at the discretion of the attending service and hyperlactatemia was defined by a lactate level > 2 mmol/L.

Results

A total of 13,932 ICU admissions occurred among 11,581 patients. The median age was 63 years (37% female), the mean APACHE II score was 25 ± 9 (n = 13,922). At presentation (within first day of admission), 12,246 patients had at least one lactate determination and the median peak lactate was 1.8 (IQR 1.2 to 2.9) mmol/L. The cumulative incidence of at least one documented episode of hyperlactatemia was 5578/13,932 (40%); 5058 (36%) patients had hyperlactatemia at presentation, and a further 520 (4%) developed hyperlactatemia subsequently. The incidence of hyperlactatemia varied significantly by major admitting diagnostic category (P < 0.001) and was highest among neuro/trauma patients 1053/2328 (45%), followed by medical 2047/4935 (41%), other surgical 900/2274 (40%), and cardiac surgical 1578/4395 (36%). Among a cohort of 9107 first admissions with ICU stay of at least one day, both hyperlactatemia at presentation (712/3634 (20%) vs. 289/5473 (5%); P < 0.001) and its later development (101/379 (27%) vs. 188/5094 (4%); P < 0.001) were associated with significantly increased case fatality rates as compared with patients without elevated lactate. After controlling for confounding effects in multivariable logistic regression analysis, hyperlactatemia was an independent risk factor for death.

Conclusions

Hyperlactatemia is common among the critically ill and predicts risk for death.