Association of macrosomia with perinatal and postneonatal mortality among First Nations people in Quebec

Background

High prevalence of infant macrosomia (up to 36%, the highest in the world) has been reported in some First Nations communities in the Canadian province of Quebec and the eastern area of the province of Ontario. We aimed to assess whether infant macrosomia was associated with elevated risks of perinatal and postneonatal mortality among First Nations people in Quebec.

Methods

We calculated risk ratios (RRs) of perinatal and postneonatal mortality by birthweight for gestational age, comparing births to First Nations women (n = 5193) versus women whose mother tongue is French (n = 653 424, the majority reference group) in Quebec 1991–2000.

Results

The prevalence of infant macrosomia (birthweight for gestational age > 90th percentile) was 27.5% among births to First Nations women, which was 3.3 times (confidence interval [CI] 3.2–3.5) higher than the prevalence (8.3%) among births to women whose mother tongue is French. Risk ratios for perinatal mortality among births to First Nations women were 1.8 (95% CI 1.3–2.5) for births with weight appropriate for gestational age, 4.1 (95% CI 2.4–7.0) for small-for-gestational-age (< 10th percentile) births and < 1 (not significant) for macrosomic births compared to births among women whose mother tongue is French. The RRs for postneonatal mortality were 4.3 (95% CI 2.7–6.7) for infants with appropriate-for-gestational-age birthweight and 8.3 (95% CI 4.0–17.0) for infants with macrosomia.

Interpretation

Macrosomia was associated with a generally protective effect against perinatal death, but substantially greater risks of postneonatal death among births to First Nations women in Quebec versus women whose mother tongue is French.A trend toward higher birthweights has emerged in recent decades.^1–3 Reflected in this trend is a rise in the prevalence of infant macrosomia, commonly defined as either a birthweight greater than 4000 g or a birthweight for gestational age greater than the 90th percentile relative to a fetal growth standard.^4–8 Maternal obesity, impaired glucose tolerance and gestational diabetes mellitus are important risk factors for infant macrosomia^9,10 and are known to afflict a much higher proportion of people in Aboriginal populations than in the general population.^11–14 This is true especially for Aboriginal populations in which a traditional lifestyle has changed to a less physically active, modern lifestyle in recent decades. A high prevalence of infant macrosomia (up to 36%, which, to the best of our knowledge, is the highest in the world) has been reported in some First Nations communities of Quebec and eastern Ontario in Canada.^15–17 However, little is known about the implications of this high prevalence for perinatal and infant health of First Nations people in these regions. We examined whether infant macrosomia was associated with increased risk for perinatal and postneonatal death among First Nations infants in Quebec.     

Adverse outcomes among Aboriginal patients receiving peritoneal dialysis

Background

The Aboriginal population in Canada experiences high rates of end-stage renal disease and need for dialytic therapies. Our objective was to examine rates of mortality, technique failure and peritonitis among adult aboriginal patients receiving peritoneal dialysis in the province of Manitoba. We also aimed to explore whether differences in these rates may be accounted for by location of residence (i.e., urban versus rural).

Methods

We included all adult patients residing in the province of Manitoba who received peritoneal dialysis during the period from 1997–2007 (n = 727). We extracted data from a local administrative database and from the Canadian Organ Replacement Registry and the Peritonitis Organism Exit-sites/Tunnel infections (POET) database. We used Cox and logistic regression models to determine the relationship between outcomes and Aboriginal ethnicity. We performed Kaplan–Meier analyses to examine the relationship between outcomes and urban (i.e., 50 km or less from the primary dialysis centre in Winnipeg) versus rural (i.e., more than 50 km from the centre) residency among patients who were aboriginal.

Results

One hundred sixty-one Aboriginal and 566 non-Aboriginal patients were included in the analyses. Adjusted hazard ratios for mortality (HR 1.476, CI 1.073–2.030) and adjusted time to peritonitis (HR 1.785, CI 1.352–2.357) were significantly higher among Aboriginal patients than among non-Aboriginal patients. We found no significant differences in mortality, technique failure or peritonitis between urban- or rural-residing Aboriginal patients.

Interpretation

Compared with non-Aboriginal patients receiving peritoneal dialysis, Aboriginal patients receiving peritoneal dialysis had higher mortality and faster time to peritonitis independent of comorbidities and demographic characteristics. This effect was not influenced by place of residence, whether rural or urban.The Canadian Aboriginal population suffers from a high burden of illness,^1,2 low socio-economic status and geographic isolation.³ A high prevalence of diabetes mellitus, obesity and hypertension in this population is resulting in rapid growth in rates of kidney disease and renal failure (i.e., end-stage renal disease).^4–6 The escalation in demand for dialytic services and care of patients with end-stage renal disease care will require appropriate planning and allocation of health care resources.Hemodialysis is resource-intensive and requires residence in proximity to a dialysis centre. In Canada, roughly 18% of all dialysis patients are receiving peritoneal dialysis.⁷ These patients are responsible for their own dialysis therapy and are seen periodically in an ambulatory clinic setting. No clear mortality-related benefit is associated with choice in modality of dialysis; each method has its own risks and benefits.^8–10 Complications of peritoneal dialysis include technique failure, which often requires conversion to hemodialysis and relocation of the patient, and peritonitis.Dosage of peritoneal dialysis is determined by the combined clearance of solutes from the peritoneum (termed the peritoneal Kt/V) and, if applicable, by residual renal function (termed renal Kt/V). The peritoneal equilibration test is a marker of the peritoneal membranes solute transport characteristics and high peritoneal equilibration test values have been associated with inflammation, volume overload, technique failure and mortality.¹¹Compared with non-Aboriginal patients who have end-stage renal disease, Aboriginal patients with end-stage renal disease are younger on average and more likely to reside in geographically remote locations.¹² Use of home-based dialysis modalities, such as peritoneal dialysis, would be well suited to this population because it allows patients to continue to live in their communities. However, residing far from a dialysis centre or a patient’s primary nephrologist is associated with increased mortality, poor compliance and impaired quality of life.^12,13 Previous studies have found that Aboriginal patients receiving peritoneal dialysis have similar mortality and rates of technique failure to patients of other ethnicities. But whether this is true in a contemporary cohort is not known.^14,15Our objective was to examine differences in mortality and in rates of technique failure and peritonitis among Aboriginal patients versus non-Aboriginal patients receiving peritoneal dialysis and to explore whether differences may be accounted for by urban versus rural residence.     

Recent epidemiologic trends of diabetes mellitus among status Aboriginal adults

Background:

Little is known about longitudinal trends in diabetes mellitus among Aboriginal people in Canada. We compared the incidence and prevalence of diabetes, and its impact on mortality, among status Aboriginal adults and adults in the general population between 1995 and 2007.

Methods:

We examined de-identified data from Alberta Health and Wellness administrative databases for status Aboriginal people (First Nations and Inuit people with treaty status) and members of the general public aged 20 years and older who received a diagnosis of diabetes mellitus from Apr. 1, 1995, to Mar. 31, 2007. We calculated the incidence and prevalence of diabetes and mortality rate ratios by sex and ethnicity in 2007. We examined the average relative changes per year for longitudinal trends.

Results:

The average relative change per year in the prevalence of diabetes showed a smaller increase over time in the Aboriginal population than in the general population (2.39 v. 4.09, p < 0.001). A similar finding was observed for the incidence of diabetes. In the Aboriginal population, we found that the increase in the average relative change per year was greater among men than among women (3.13 v. 1.88 for prevalence, p < 0.001; 2.60 v. 0.02 for incidence, p = 0.001). Mortality among people with diabetes decreased over time to a similar extent in both populations. Among people without diabetes, mortality decreased in the general population but was unchanged in the Aboriginal population (−1.92 v. 0.11, p = 0.04). Overall, mortality was higher in the Aboriginal population than in the general population regardless of diabetes status.

Interpretation:

The increases in the incidence and prevalence of diabetes over the study period appeared to be slower in the status Aboriginal population than in the general population in Alberta, although the overall rates were higher in the Aboriginal population. Mortality decreased among people with diabetes in both populations but was higher overall in the Aboriginal population regardless of diabetes status.The health of Aboriginal people in Canada is generally poorer than their non-Aboriginal counterparts, and diabetes mellitus is a significant contributor.^1,2 Studies have shown that type 2 diabetes and its complications occur at rates two to five times higher in Canada’s Aboriginal population than in the general population.^3–7 In response, diverse diabetes programs have materialized, including various community-based prevention and screening projects.^8–10 The federally funded Aboriginal Diabetes Initiative was created to emphasize health promotion and diabetes prevention.¹¹ In addition, numerous Aboriginal communities have established their own diabetes and health programs.¹²Accurate diabetes surveillance data are essential for governments and health care organizations to plan health care delivery and translate knowledge into policy and funding decisions. However, research into the longitudinal trends of diabetes in Aboriginal populations is scarce. For the most part, data have come from small, community-based studies and self-reported surveys. Population-based studies of primary data are few and have been conducted only for limited periods. Even less is known about outcomes, mortality in particular, among Aboriginal individuals with diabetes.The use of administrative data is becoming more common for tracking diabetes in Canada.¹³ The National Diabetes Surveillance System uses administrative health data to document the burden of the disease, but it has little information on Aboriginal people. Dyck and colleagues recently used the methodology of the National Diabetes Surveillance System to examine the incidence and prevalence of diabetes among Aboriginal people in the province of Saskatchewan,¹⁴ and similar analyses were conducted in Manitoba and Ontario.^15,16As part of the Alberta Diabetes Surveillance System, we conducted this study to compare the incidence and prevalence of diabetes among people 20 years and older in the status Aboriginal population (First Nations and Inuit people with treaty status) and the general population in the province of Alberta between 1995 and 2007. We also compared trends in mortality in the two populations among people with and without diabetes.     

Epidemiology of diabetes mellitus among First Nations and non-First Nations adults

Background

First Nations people in Canada experience a disproportionate burden of type 2 diabetes mellitus. To increase our understanding of this evolving epidemic, we compared the epidemiology of diabetes between First Nations and non-First Nations adults in Saskatchewan from 1980 to 2005.

Methods

We used administrative databases to perform a population-based study of diabetes frequency, incidence and prevalence in adults by ethnic background, year, age and sex.

Results

We identified 8275 First Nations and 82 306 non-First Nations people with diabetes from 1980 to 2005. Overall, the incidence and prevalence of diabetes were more than 4 times higher among First Nations women than among non-First Nations women and more than 2.5 times higher among First Nations men than among non-First Nations men. The number of incident cases of diabetes was highest among First Nations people aged 40–49 , while the number among non-First Nations people was greatest in those aged 70 or more years. The prevalence of diabetes increased over the study period from 9.5% to 20.3% among First Nations women and from 4.9% to 16.0% among First Nations men. Among non-First Nations people, the prevalence increased from 2.0% to 5.5% among women and from 2.0% to 6.2% among men. By 2005, almost 50% of First Nations women and more than 40% of First Nations men aged 60 or older had diabetes, compared with less than 25% of non-First Nations men and less than 20% of non-First Nations women aged 80 or older.

Interpretation

First Nations adults are experiencing a diabetes epidemic that disproportionately affects women during their reproductive years. This ethnicity-based pattern suggests diverse underlying mechanisms that may include differences in the diabetogenic impact of gestational diabetes.The global epidemic of type 2 diabetes mellitus disproportionately affects indigenous and developing populations.¹ Although genotypic variants related to energy balance may underlie this epidemic,² the rapid emergence of type 2 diabetes in genetically diverse populations worldwide is most likely caused by environmental factors. Increasing rates of type 2 diabetes among Canada’s First Nations people, for example, parallel an epidemic of overweight and obesity that has coincided with socio-cultural disruption and a loss of traditional lifestyles.³In Saskatchewan in 1937, diabetes was not detected among the 1500 First Nations people who underwent a tuberculosis survey.⁴ By 1990, almost 10% of the province’s First Nations adults had diabetes;⁵ by 2006, the proportion was over 20%,⁶ while it remained at about 6% in the general population.^5,6 Although an increased prevalence of diabetes among First Nations people has also been documented in other Canadian provinces,³ only recently have consistent diabetes case definitions applied to health care system administrative databases been used to compare differences between large populations of First Nations and non-First Nations people.^7–9We sought to describe the epidemiology of diabetes in Saskatchewan from 1980 to 2005. We reasoned that finding ethnicity-based differences in trends and patterns of type 2 diabetes over the longest period reported for a Canadian jurisdiction would help to clarify the underlying mechanisms behind known disparities and translate into more effective diabetes prevention and management initiatives.     

Differential mortality and the excess burden of end-stage renal disease among First Nations people with diabetes mellitus: a competing-risks analysis

Background:

Diabetes-related end-stage renal disease disproportionately affects indigenous peoples. We explored the role of differential mortality in this disparity.

Methods:

In this retrospective cohort study, we examined the competing risks of end-stage renal disease and death without end-stage renal disease among Saskatchewan adults with diabetes mellitus, both First Nations and non–First Nations, from 1980 to 2005. Using administrative databases of the Saskatchewan Ministry of Health, we developed Fine and Gray subdistribution hazards models and cumulative incidence functions.

Results:

Of the 90 429 incident cases of diabetes, 8254 (8.9%) occurred among First Nations adults and 82 175 (90.9%) among non–First Nations adults. Mean age at the time that diabetes was diagnosed was 47.2 and 61.6 years, respectively (p < 0.001). After adjustment for sex and age at the time of diabetes diagnosis, the risk of end-stage renal disease was 2.66 times higher for First Nations than non–First Nations adults (95% confidence interval [CI] 2.24–3.16). Multivariable analysis with adjustment for sex showed a higher risk of death among First Nations adults, which declined with increasing age at the time of diabetes diagnosis. Cumulative incidence function curves stratified by age at the time of diabetes diagnosis showed greatest risk for end-stage renal disease among those with onset of diabetes at younger ages and greatest risk of death among those with onset of diabetes at older ages.

Interpretation:

Because they are typically younger when diabetes is diagnosed, First Nations adults with this condition are more likely than their non–First Nations counterparts to survive long enough for end-stage renal disease to develop. Differential mortality contributes substantially to ethnicity-based disparities in diabetes-related end-stage renal disease and possibly to chronic diabetes complications. Understanding the mechanisms underlying these disparities is vital in developing more effective prevention and management initiatives.Indigenous peoples experience an excess burden of diabetes-related end-stage renal disease,^1–4 but the reasons for this disparity are incompletely understood. Although the increase in end-stage renal disease among indigenous peoples has paralleled the global emergence of type 2 diabetes mellitus,⁵ disparities in end-stage renal disease among Canada’s First Nations adults persist² after adjustment for elevated prevalence of diabetes.⁶ In an earlier study, we suggested that First Nations adults might be more prone to diabetic nephropathy and might experience more rapid progression to end-stage renal disease.⁷ However, although albuminuria is more prevalent in this population,⁸ affected individuals unexpectedly have a longer average time from diagnosis of diabetes to end-stage renal disease than people from non–First Nations populations.² These findings could be explained by a younger age at the time of diabetes diagnosis⁶ and lower mortality among those with chronic kidney disease.⁸ An age-related survival benefit among First Nations adults with diabetes could lead to longer exposure to the metabolic consequences of diabetes and greater likelihood of end-stage renal disease.Our objective was to examine the contribution of differential mortality to disparities in diabetes-related end-stage renal disease within large populations of indigenous and non-indigenous North Americans. Accordingly, we used competing-risks survival analysis to compare the simultaneous risks of diabetes-related end-stage renal disease and death without end-stage renal disease among First Nations and non–First Nations adults.⁹     

Tobacco, alcohol and illicit drug use among Aboriginal youth living off-reserve: results from the Youth Smoking Survey

Background

Despite the high prevalence of smoking among Aboriginal youth, there is a paucity of research related to tobacco use and other risk behaviours among Aboriginal youth living off-reserve in Canada. We used data from the national Youth Smoking Survey to characterize non-traditional tobacco use, exposure to second-hand smoke, and alcohol and drug use among Aboriginal youth living off-reserve. We examined whether these youth were at increased health risk compared with non-Aboriginal youth.

Methods

We examined cigarette smoking behaviour, use of other tobacco products, use of alcohol and other drugs, and exposure to second-hand smoke among 2620 Aboriginal youth living off-reserve and 26 223 non-Aboriginal youth in grades 9 to 12 who participated in the 2008/09 Youth Smoking Survey.

Results

The prevalence of current smoking among the Aboriginal youth was more than double that among non-Aboriginal youth (24.9% v. 10.4%). Aboriginal youth also had a higher prevalence of regular exposure to second-hand smoke at home (37.3% v. 19.7%) and in cars (51.0% v. 30.3%). Aboriginal youth were more likely than non-Aboriginal youth to be current smokers, to be regularly exposed to second-hand smoke, to have tried marijuana and other illicit drugs, and to engage in binge drinking. They were less likely than non-Aboriginal youth to have tried to quit smoking.

Interpretation

Current national estimates of smoking, and alcohol and illicit drug use among youth underestimate the prevalence of these behaviours among Aboriginal youth living off-reserve. Our findings highlight the need for culturally appropriate prevention and cessation policies and programs for this at-risk population.Compared with the general population in Canada, Aboriginal youth start smoking earlier¹ and have a higher prevalence of smoking,^1–3 with female Aboriginals at greatest risk.¹ Research has also shown that Aboriginal youth have high rates of binge drinking¹ and are more likely than non-Aboriginal youth to use marijuana.⁴Despite the high prevalence of smoking among Aboriginal youth in Canada, there is a paucity of research related to their patterns of tobacco use, especially among Aboriginals living off-reserve.⁵ Most Aboriginals in Canada live off-reserve,⁶ and those 15 years of age and older are more likely than non-Aboriginals to have chronic health conditions, to drink heavily and to smoke.⁷ Given that the Canadian Tobacco Control Strategy emphasizes targeting youth, young adults, First Nations, Inuit and other Aboriginal groups,⁸ a better understanding of tobacco use among Aboriginal youth living off-reserve is required.We conducted this study to examine patterns of tobacco use, exposure to second-hand smoke and the prevalence of alcohol and other drug use among Aboriginal youth living off-reserve. We compared these data with those for non-Aboriginal youth using nationally representative data from the 2008/09 Youth Smoking Survey.     

Likelihood of coronary angiography among First Nations patients with acute myocardial infarction

Background:

Morbidity due to cardiovascular disease is high among First Nations people. The extent to which this may be related to the likelihood of coronary angiography is unclear. We examined the likelihood of coronary angiography after acute myocardial infarction (MI) among First Nations and non–First Nations patients.

Methods:

Our study included adults with incident acute MI between 1997 and 2008 in Alberta. We determined the likelihood of angiography among First Nations and non–First Nations patients, adjusted for important confounders, using the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH) database.

Results:

Of the 46 764 people with acute MI, 1043 (2.2%) were First Nations. First Nations patients were less likely to receive angiography within 1 day after acute MI (adjusted odds ratio [OR] 0.73, 95% confidence interval [CI] 0.62–0.87). Among First Nations and non–First Nations patients who underwent angiography (64.9%), there was no difference in the likelihood of percutaneous coronary intervention (PCI) (adjusted hazard ratio [HR] 0.92, 95% CI 0.83–1.02) or coronary artery bypass grafting (CABG) (adjusted HR 1.03, 95% CI 0.85–1.25). First Nations people had worse survival if they received medical management alone (adjusted HR 1.38, 95% CI 1.07–1.77) or if they underwent PCI (adjusted HR 1.38, 95% CI 1.06–1.80), whereas survival was similar among First Nations and non–First Nations patients who received CABG.

Interpretation:

First Nations people were less likely to undergo angiography after acute MI and experienced worse long-term survival compared with non–First Nations people. Efforts to improve access to angiography for First Nations people may improve outcomes.Although cardiovascular disease has been decreasing in Canada,¹ First Nations people have a disproportionate burden of the disease. First Nations people in Canada have a 2.5-fold higher prevalence of cardiovascular disease than non–First Nations people,² with hospital admissions for cardiovascular-related events also increasing.³The prevalence of cardiovascular disease in First Nations populations is presumed to be reflective of the prevalence of cardiovascular risk factors.^4–7 However, the disproportionate increase in rates of hospital admission suggests that suboptimal management of cardiovascular disease or its risk factors may also influence patient outcomes.^2,3 Racial disparities in the quality of cardiovascular care resulting in adverse outcomes have been documented, although most studies have focused on African-American, Hispanic and Asian populations.^8,9 As a result, it is unclear whether suboptimal delivery of guideline-recommended treatment contributes to increased cardiovascular morbidity and mortality among First Nations people.^10–12We undertook a population-based study involving adults with incident acute myocardial infarction (MI) to examine the receipt of guideline-recommended coronary angiography among First Nations and non–First Nations patients.^10–12 Among patients who underwent angiography, we sought to determine whether there were differences between First Nations and non–First Nations patients in the likelihood of revascularization and long-term survival.     

Utility of prior screening for methicillin-resistant Staphylococcus aureus in predicting resistance of S. aureus infections

Background:

Screening for methicillin-resistant Staphylococcus aureus (MRSA) is intended to reduce nosocomial spread by identifying patients colonized by MRSA. Given the widespread use of this screening, we evaluated its potential clinical utility in predicting the resistance of clinical isolates of S. aureus.

Methods:

We conducted a 2-year retrospective cohort study that included patients with documented clinical infection with S. aureus and prior screening for MRSA. We determined test characteristics, including sensitivity and specificity, of screening for predicting the resistance of subsequent S. aureus isolates.

Results:

Of 510 patients included in the study, 53 (10%) had positive results from MRSA screening, and 79 (15%) of infecting isolates were resistant to methicillin. Screening for MRSA predicted methicillin resistance of the infecting isolate with 99% (95% confidence interval [CI] 98%–100%) specificity and 63% (95% CI 52%–74%) sensitivity. When screening swabs were obtained within 48 hours before isolate collection, sensitivity increased to 91% (95% CI 71%–99%) and specificity was 100% (95% CI 97%–100%), yielding a negative likelihood ratio of 0.09 (95% CI 0.01–0.3) and a negative predictive value of 98% (95% CI 95%–100%). The time between swab and isolate collection was a significant predictor of concordance of methicillin resistance in swabs and isolates (odds ratio 6.6, 95% CI 1.6–28.2).

Interpretation:

A positive result from MRSA screening predicted methicillin resistance in a culture-positive clinical infection with S. aureus. Negative results on MRSA screening were most useful for excluding methicillin resistance of a subsequent infection with S. aureus when the screening swab was obtained within 48 hours before collection of the clinical isolate.Antimicrobial resistance is a global problem. The prevalence of resistant bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), has reached high levels in many countries.^1–3 Methicillin resistance in S. aureus is associated with excess mortality, hospital stays and health care costs,^3,4 possibly owing to increased virulence or less effective treatments for MRSA compared with methicillin-sensitive S. aureus (MSSA).⁵The initial selection of appropriate empirical antibiotic treatment affects mortality, morbidity and potential health care expenditures.^6–8 The optimal choice of antibiotics in S. aureus infections is important for 3 major reasons: β-lactam antibiotics have shown improved efficacy over vancomycin and are the ideal treatment for susceptible strains of S. aureus;⁶ β-lactam antibiotics are ineffective against MRSA, and so vancomycin or other newer agents must be used empirically when MRSA is suspected; and unnecessary use of broad-spectrum antibiotics (e.g., vancomycin) can lead to the development of further antimicrobial resistance.⁹ It is therefore necessary to make informed decisions regarding selection of empirical antibiotics.^10–13 Consideration of a patient’s previous colonization status is important, because colonization predates most hospital and community-acquired infections.^10,14Universal or targeted surveillance for MRSA has been implemented widely as a means of limiting transmission of this antibiotic-resistant pathogen.^15,16 Although results of MRSA screening are not intended to guide empirical treatment, they may offer an additional benefit among patients in whom clinical infection with S. aureus develops.Studies that examined the effects of MRSA carriage on the subsequent likelihood of infection allude to the potential diagnostic benefit of prior screening for MRSA.^17,18 Colonization by MRSA at the time of hospital admission is associated with a 13-fold increased risk of subsequent MRSA infection.^17,18 Moreover, studies that examined nasal carriage of S. aureus after documented S. aureus bacteremia have shown remarkable concordance between the genotypes of paired colonizing and invasive strains (82%–94%).^19,20 The purpose of our study was to identify the usefulness of prior screening for MRSA for predicting methicillin resistance in culture-positive S. aureus infections.     

The responses of Aboriginal Canadians to adjuvanted pandemic (H1N1) 2009 influenza vaccine

Background:

Because many Aboriginal Canadians had severe cases of pandemic (H1N1) 2009 influenza, they were given priority access to vaccine. However, it was not known if the single recommended dose would adequately protect people at high risk, prompting our study to assess responses to the vaccine among Aboriginal Canadians.

Methods:

We enrolled First Nations and Métis adults aged 20–59 years in our prospective cohort study. Participants were given one 0.5-mL dose of ASO3-adjuvanted pandemic (H1N1) 2009 vaccine (Arepanrix, GlaxoSmithKline Canada). Blood samples were taken at baseline and 21–28 days after vaccination. Paired sera were tested for hemagglutination-inhibiting antibodies at a reference laboratory. To assess vaccine safety, we monitored the injection site symptoms of each participant for seven days. We also monitored patients for general symptoms within 7 days of vaccination and any use of the health care system for 21–28 days after vaccination.

Results:

We enrolled 138 participants in the study (95 First Nations, 43 Métis), 137 of whom provided all safety data and 136 of whom provided both blood samples. First Nations and Métis participants had similar characteristics, including high rates of chronic health conditions (74.4%–76.8%). Pre-existing antibody to the virus was detected in 34.3% of the participants, all of whom boosted strongly with vaccination (seroprotection rate [titre ≥ 40] 100%, geometric mean titre 531–667). Particpants with no pre-existing antibody also responded well. Fifty-eight of 59 (98.3%) First Nations participants showed seroprotection and a geometric mean titre of 353.6; all 30 Métis participants with no pre-existing antibody showed seroprotection and a geometric mean titre of 376.2. Pain at the injection site and general symptoms frequently occurred but were short-lived and generally not severe, although three participants (2.2%) sought medical attention for general symptoms.

Interpretation:

First Nations and Métis adults responded robustly to ASO3-adjuvanted pandemic (H1N1) 2009 vaccine. Virtually all participants showed protective titres, including those with chronic health conditions.

Trial registration:

ClinicalTrials.gov trial register no. NCT.01001026.During the first wave of the H1N1 pandemic in Canada in 2009, some First Nations communities were severely affected, with younger adults and children most at risk for severe disease.^1,2 Whereas Aboriginal Canadians make up 3.4% of the population (with 1.14 million people), they accounted for 16% of admissions to hospital during the first wave of the pandemic, and 43% of Aboriginal patients had underlying medical conditions.³ The increased rate of severe disease might have resulted from residential crowding, prevalence of chronic health conditions, delayed access to health care or suboptimal immune responses to infection.⁴ When a federally funded, ASO3-adjuvanted (squalene/tocopherol) pandemic vaccine became available for Canadians later in 2009,⁵ Aboriginal people were given priority access to it.³ However, dosing requirements at the time were tentative. Previous studies of an ASO3-adjuvanted influenza A (H5N1) vaccine established that two doses were needed for immunity in adults.⁶ Because the 2009 influenza (H1N1) pandemic occurred without warning, no prepandemic studies had been done with vaccines based on this novel swine-derived virus.⁷The ASO3-adjuvanted pandemic (H1N1) 2009 vaccine manufactured in Canada (Arepanrix, GlaxoSmithKline, Laval, Quebec) was released for public use as soon as it was available, unstudied, to mitigate morbidity during the pandemic’s second wave, which was already in progress. A single 3.75-μg dose of hemagglutinin was recommended for adults using the preliminary results of a European trial of another ASO3-adjuvanted vaccine (Pandemrix, GlaxoSmithKline, Rixensart, Belgium) given to 65 adults aged 18–60 years.⁸ The European product was believed to be equivalent to the Canadian-made vaccine, but this had not yet been shown.We wondered if the recommended single dose would be adequate for Aboriginal Canadian adults given their heightened risk of severe influenza during the first wave. We were unable to identify any previous studies of influenza vaccines involving Aboriginal Canadians to determine if their responses would be similar to other Canadians or to the healthy European study participants on whom the dosing recommendation was based. Consequently, we undertook a study involving First Nations and Métis adults to assess their responses to the pandemic vaccine.     

Dialysis and transplantation among Aboriginal children with kidney failure

Background:

Relatively little is known about the management and outcomes of Aboriginal children with renal failure in Canada. We evaluated differences in dialysis modality, time spent on dialysis, rates of kidney transplantation, and patient and allograft survival between Aboriginal children and non-Aboriginal children.

Methods:

For this population-based cohort study, we used data from a national pediatric end-stage renal disease database. Patients less than 18 years old who started renal replacement treatment (dialysis or kidney transplantation) in nine Canadian provinces (Quebec data were not available) and all three territories between 1992 and 2007 were followed until death, loss to follow-up or end of the study period. We compared initial modality of dialysis and time to first kidney transplant between Aboriginal children, white children and children of other ethnicity. We examined the association between ethnicity and likelihood of kidney transplantation using adjusted Cox proportional hazard models for Aboriginal and white children (data for the children of other ethnicity did not meet the assumptions of proportional hazards).

Results:

Among 843 pediatric patients included in the study, 104 (12.3%) were Aboriginal, 521 (61.8%) were white, and 218 (25.9%) were from other ethnic minorities. Hemodialysis was the initial modality of dialysis for 48.0% of the Aboriginal patients, 42.7% of the white patients and 62.6% of those of other ethnicity (p < 0.001). The time from start of dialysis to first kidney transplant was longer among the Aboriginal children (median 1.75 years, interquartile range 0.69–2.81) than among the children in the other two groups (p < 0.001). After adjustment for confounders, Aboriginal children were less likely than white children to receive a transplant from a living donor (hazard ratio [HR] 0.36, 95% confidence interval [CI] 0.21–0.61) or a transplant from any donor (HR 0.54, 95% CI 0.40–0.74) during the study period.

Interpretation:

The time from start of dialysis to first kidney transplant was longer among Aboriginal children than among white children. Further evaluation is needed to determine barriers to transplantation among Aboriginal children.Compared with non-Aboriginal people, Aboriginal adults with end-stage renal disease in Canada have lower rates of kidney transplantation, the optimal treatment for renal failure.^1–4 Most studies to date that have examined health outcomes among Canadian Aboriginal people with kidney disease have focused on adults.^1–8 Relatively little is known about the outcomes among Aboriginal children with renal failure. A single-centre cohort study from the province of British Columbia reported that Aboriginal children who received a kidney transplant had similar short-term, but poorer long-term allograft survival than white children.⁹ No further studies have examined differences in modality of renal replacement treatment or the likelihood of kidney transplantation among Aboriginal children with renal failure.We performed an observational cohort study of children beginning renal replacement treatment in Canada. We compared differences in dialysis modality, time spent on dialysis, rates of kidney transplantation, and graft and patient survival between Aboriginal children, white children and children of other ethnicities.     

Association between First Nations ethnicity and progression to kidney failure by presence and severity of albuminuria

Background:

Despite a low prevalence of chronic kidney disease (estimated glomerular filtration rate [GFR] < 60 mL/min per 1.73 m²), First Nations people have high rates of kidney failure requiring chronic dialysis or kidney transplantation. We sought to examine whether the presence and severity of albuminuria contributes to the progression of chronic kidney disease to kidney failure among First Nations people.

Methods:

We identified all adult residents of Alberta (age ≥ 18 yr) for whom an outpatient serum creatinine measurement was available from May 1, 2002, to Mar. 31, 2008. We determined albuminuria using urine dipsticks and categorized results as normal (i.e., no albuminuria), mild, heavy or unmeasured. Our primary outcome was progression to kidney failure (defined as the need for chronic dialysis or kidney transplantation, or a sustained doubling of serum creatinine levels). We calculated rates of progression to kidney failure by First Nations status, by estimated GFR and by albuminuria category. We determined the relative hazard of progression to kidney failure for First Nations compared with non–First Nations participants by level of albuminuria and estimated GFR.

Results:

Of the 1 816 824 participants we identified, 48 669 (2.7%) were First Nations. First Nations people were less likely to have normal albuminuria compared with non–First Nations people (38.7% v. 56.4%). Rates of progression to kidney failure were consistently 2- to 3-fold higher among First Nations people than among non–First Nations people, across all levels of albuminuria and estimated GFRs. Compared with non–First Nations people, First Nations people with an estimated GFR of 15.0–29.9 mL/min per 1.73 m² had the highest risk of progression to kidney failure, with similar hazard ratios for those with normal and heavy albuminuria.

Interpretation:

Albuminuria confers a similar risk of progression to kidney failure for First Nations and non–First Nations people.Severe chronic kidney disease (estimated glomerular filtration rate [GFR] < 30 mL/min per 1.73 m²) is almost 2-fold higher, and rates of end-stage kidney disease (defined as the need for chronic dialysis or kidney transplantation) are 4-fold higher, among First Nations people compared with non–First Nations people in Canada.^1,2 The reasons for the higher rate of end-stage kidney disease when there is a lower prevalence of earlier stages of chronic kidney disease in First Nations people (estimated GFR 30–60 mL/min per 1.73 m²) are unclear. The rising incidence of diabetes is seen as the major cause of kidney failure among First Nations people;³ however, First Nations people without diabetes are also 2–3 times more likely to eventually have kidney failure.⁴ These observations suggest that diabetes is not the sole determinant of risk for kidney failure and that there are yet undefined factors that may accelerate the progression of chronic kidney disease in the First Nations population.⁵Recent studies have highlighted the prognostic importance of albuminuria as a risk factor for kidney failure.⁶ Although ethnic variations in the prevalence and severity of albuminuria and their association with renal outcomes have been reported, these studies are primarily limited to non–First Nations populations.⁷ A limited number of studies have reported an increased prevalence of albuminuria among First Nations people, suggesting the potential association between albuminuria and risk of kidney failure.^8,9 We sought to measure the presence and severity of albuminuria and estimate the risk of progression to kidney failure for First Nations people compared with non–First Nations people using a community-based cohort.     

A prospective cohort study of pregnancy risk factors and birth outcomes in Aboriginal women

Background

Aboriginal women have been identified as having poorer pregnancy outcomes than other Canadian women, but information on risk factors and outcomes has been acquired mostly from retrospective databases. We compared prenatal risk factors and birth outcomes of First Nations and Métis women with those of other participants in a prospective study.

Methods

During the 12-month period from July 1994 to June 1995, we invited expectant mothers in all obstetric practices affiliated with a single teaching hospital in Edmonton to participate. Women were recruited at their first prenatal visit and followed through delivery. Sociodemographic and clinical data were obtained by means of a patient questionnaire, and microbiological data were collected at 3 points during gestation: in the first and second trimesters and during labour. Our primary outcomes of interest were low birth weight (birth weight less than 2500 g), prematurity (birth at less than 37 weeks'' gestation) and macrosomia (birth weight greater than 4000 g).

Results

Of the 2047 women consecutively enrolled, 1811 completed the study through delivery. Aboriginal women accounted for 70 (3.9%) of the subjects who completed the study (45 First Nations women and 25 Métis women). Known risk factors for adverse pregnancy outcome were more common among Aboriginal than among non-Aboriginal women, including previous premature infant (21% v. 11%), smoking during the current pregnancy (41% v. 13%), presence of bacterial vaginosis in midgestation (33% v. 13%) and poor nutrition as measured by meal consumption. Although Aboriginal women were less likely than non-Aboriginal women to have babies of low birth weight (odds ratio [OR] 1.46, 95% confidence interval [CI] 0.52–4.15) or who were born prematurely (OR 1.45, 95% CI 0.57–3.72) and more likely to have babies with macrosomia (OR 2.04, 95% CI 1.03–4.03), these differences were lower and statistically nonsignificant after adjustment for smoking, cervicovaginal infection and income (adjusted OR for low birth weight 0.85, 95% CI 0.19–3.78; for prematurity 0.90, 95% CI 0.21–3.89; and for macrosomia 2.12, 95% CI 0.84-5.36).

Interpretation

After adjustment for potential confounding factors, we found no statistically significant relation between Aboriginal status and birth outcome.It is generally recognized that Aboriginal women experience poorer birth outcomes than other North American women, including higher rates of stillbirth,¹ low-birth-weight infants^1,2,3 and prematurity.^2,3 Although significant efforts have been made to reduce Aboriginal infant mortality rates, these rates remain higher than for other infants in both Canada⁴ and the United States.⁵ Little is known about the reasons for differences in birth outcomes, although social, economic, medical and prenatal care factors have been suggested. Recent publications, based on retrospective analyses of large databases, have confirmed disparities in birth outcomes between Aboriginal and all other groups,^3,6,7 but there is a paucity of prospective data. In addition, although the term “Aboriginal” refers to a heterogeneous population comprising First Nations people, Métis and Inuit, there are few comparisons between specific Aboriginal groups or of Aboriginal groups with the general population.We report here the results of a prospective study in a general obstetric population, comparing birth outcomes and known pregnancy risk factors of Aboriginal women with those of non-Aboriginal Canadian women. In addition to well-recognized socioeconomic and reproductive risk factors, we investigated the prevalence of maternal cervicovaginal infections, which have been increasingly linked to prematurity.^8,9     

Incidence and causes of end-stage renal disease among Aboriginal children and young adults

Background:

Although Aboriginal adults have a higher risk of end-stage renal disease than non-Aboriginal adults, the incidence and causes of end-stage renal disease among Aboriginal children and young adults are not well described.

Methods:

We calculated age- and sex-specific incidences of end-stage renal disease among Aboriginal people less than 22 years of age using data from a national organ failure registry. Incidence rate ratios were used to compare rates between Aboriginal and white Canadians. To contrast causes of end-stage renal disease by ethnicity and age, we calculated the odds of congenital diseases, glomerulonephritis and diabetes for Aboriginal people and compared them with those for white people in the following age strata: 0 to less than 22 years, 22 to less than 40 years, 40 to less than 60 years and older than 60 years.

Results:

Incidence rate ratios of end-stage renal disease for Aboriginal children and young adults (age < 22 yr, v. white people) were 1.82 (95% confidence interval [CI] 1.40–2.38) for boys and 3.24 (95% CI 2.60–4.05) for girls. Compared with white people, congenital diseases were less common among Aboriginal people aged less than 22 years (odds ratio [OR] 0.56, 95% CI 0.36–0.86), and glomerulonephritis was more common (OR 2.18, 95% CI 1.55–3.07). An excess of glomerulonephritis, but not diabetes, was seen among Aboriginal people aged 22 to less than 40 years. The converse was true (higher risk of diabetes, lower risk of glomerulonephritis) among Aboriginal people aged 40 years and older.

Interpretation:

The incidence of end-stage renal disease is higher among Aboriginal children and young adults than among white children and young adults. This higher incidence may be driven by an increased risk of glomerulonephritis in this population.Compared with white Canadians, Aboriginal Canadians have a higher prevalence of end-stage renal disease,^1,2 which is generally attributed to their increased risk for diabetes. However, there has been limited investigation of the incidence and causes of end-stage renal disease among Aboriginal children and young adults. Because most incident cases of diabetes are identified in middle-aged adults, an excess risk of end-stage renal disease in young people would not be expected if the high risk of diabetes is responsible for higher overall rates of end-stage renal disease among Aboriginal people. About 12.3% of children with end-stage renal disease in Canada are Aboriginal,³ but only 6.1% of Canadian children (age < 19 yr) are Aboriginal.^4,5A few reports suggest that nondiabetic renal disease is common among Aboriginal populations in North America.^2,6–8 Aboriginal adults in Saskatchewan are twice as likely as white adults to have end-stage renal disease caused by glomerulonephritis,^7,8 and an increased rate of mesangial proliferative glomerulonephritis has been reported among Aboriginal people in the United States.^6,9 These studies suggest that diabetes may be a comorbid condition rather than the sole cause of kidney failure among some Aboriginal people in whom diabetic nephropathy is diagnosed using clinical features alone.We estimated incidence rates of end-stage renal disease among Aboriginal children and young adults in Canada and compared them with the rates seen among white children and young adults. In addition, we compared relative odds of congenital renal disease, glomerulonephritis and diabetic nephropathy in Aboriginal people with the relative odds of these conditions in white people.     

Effect of a provincial system of stroke care delivery on stroke care and outcomes

Background:

Systems of stroke care delivery have been promoted as a means of improving the quality of stroke care, but little is known about their effectiveness. We assessed the effect of the Ontario Stroke System, a province-wide strategy of regionalized stroke care delivery, on stroke care and outcomes in Ontario, Canada.

Methods:

We used population-based provincial administrative databases to identify all emergency department visits and hospital admissions for acute stroke and transient ischemic attack from Jan. 1, 2001, to Dec. 31, 2010. Using piecewise regression analyses, we assessed the effect of the full implementation of the Ontario Stroke System in 2005 on the proportion of patients who received care at stroke centres, and on rates of discharge to long-term care facilities and 30-day mortality after stroke.

Results:

We included 243 287 visits by patients with acute stroke or transient ischemic attack. The full implementation of the Ontario Stroke System in 2005 was associated with an increase in rates of care at stroke centres (before implementation: 40.0%; after implementation: 46.5%), decreased rates of discharge to long-term care facilities (before implementation: 16.9%; after implementation: 14.8%) and decreased 30-day mortality for hemorrhagic (before implementation: 38.3%; after implementation: 34.4%) and ischemic stroke (before implementation: 16.3%; after implementation: 15.7%). The system’s implementation was also associated with marked increases in the proportion of patients who received neuroimaging, thrombolytic therapy, care in a stroke unit and antithrombotic therapy.

Interpretation:

The implementation of an organized system of stroke care delivery was associated with improved processes of care and outcomes after stroke.Stroke is a leading cause of death and disability worldwide.^1,2 Guidelines recommend that eligible patients receive care in a stroke unit, undergo neuroimaging and receive thrombolytic therapy, antithrombotic agents and screening for carotid stenosis.^3–6 Many of these interventions require specialized resources, including clinicians with expertise in stroke care and rapid access to brain and vascular imaging; however, wide interfacility variations exist in the availability of such resources.^7–10To address regional disparities in resources and care, organizations such as the Canadian Stroke Network and the American Stroke Association have recommended the implementation of organized systems of stroke care delivery.^11,12 Such systems are designed to facilitate access to optimal stroke care across an entire region and to promote the use of evidence-based therapies.¹¹ However, little is known about the effect of stroke systems of care on outcomes in patients with stroke.The province of Ontario was the first large jurisdiction in Canada, and in North America, to implement an integrated regional system of stroke care delivery. A system of coordinated stroke care, known as the Ontario Stroke System, was launched in 2000 and fully implemented in 2005, resulting in a major transformation in the delivery of stroke care across the province.¹³ We used population-based administrative and clinical data to evaluate the effect of the system’s implementation on stroke care and outcomes.     

Hypertriglyceridemic-waist phenotype and glucose intolerance among Canadian Inuit: the International Polar Year Inuit Health Survey for Adults 2007�C2008

Background

Inuit have not experienced an epidemic in type 2 diabetes mellitus, and it has been speculated that they may be protected from obesity’s metabolic consequences. We conducted a population-based screening for diabetes among Inuit in the Canadian Arctic and evaluated the association of visceral adiposity with diabetes.

Methods

A total of 36 communities participated in the International Polar Year Inuit Health Survey. Of the 2796 Inuit households approached, 1901 (68%) participated, with 2595 participants. Households were randomly selected, and adult residents were invited to participate. Assessments included anthropometry and fasting plasma lipids and glucose, and, because of survey logistics, only 32% of participants underwent a 75 g oral glucose tolerance test. We calculated weighted prevalence estimates of metabolic risk factors for all participants.

Results

Participants’ mean age was 43.3 years; 35% were obese, 43.8% had an at-risk waist, and 25% had an elevated triglyceride level. Diabetes was identified in 12.2% of participants aged 50 years and older and in 1.9% of those younger than 50 years. A hypertriglyceridemic-waist phenotype was a strong predictor of diabetes (odds ratio [OR] 8.6, 95% confidence interval [CI] 2.1–34.6) in analyses adjusted for age, sex, region, family history of diabetes, education and use of lipid-lowering medications.

Interpretation

Metabolic risk factors were prevalent among Inuit. Our results suggest that Inuit are not protected from the metabolic consequences of obesity, and that their rate of diabetes prevalence is now comparable to that observed in the general Canadian population. Assessment of waist circumference and fasting triglyceride levels could represent an efficient means for identifying Inuit at high risk for diabetes.Indigenous people across the Arctic continue to undergo cultural transitions that affect all dimensions of life, with implications for emerging obesity and changes in patterns of disease burden.^1–3 A high prevalence of obesity among Canadian Inuit has been noted,^3,4 and yet studies have suggested that the metabolic consequences of obesity may not be as severe among Inuit as they are in predominantly Caucasian or First Nations populations.^4–6 Conversely, the prevalence of type 2 diabetes mellitus, which was noted to be rare among Inuit in early studies,^7,8 now matches or exceeds that of predominately Caucasian comparison populations in Alaska and Greenland.^9–11 However, in Canada, available reports suggest that diabetes prevalence among Inuit remains below that of the general Canadian population.^3,12Given the rapid changes in the Arctic and a lack of comprehensive and uniform screening assessments, we used the International Polar Year Inuit Health Survey for Adults 2007–2008 to assess the current prevalence of glycemia and the toll of age and adiposity on glycemia in this population. However, adiposity is heterogeneous, and simple measures of body mass index (BMI) in kg/m² and waist circumference do not measure visceral adiposity (or intra-abdominal adipose tissue), which is considered more deleterious than subcutaneous fat.¹³ Therefore, we evaluated the “hypertriglyceridemic-waist” phenotype (i.e., the presence of both an at-risk waist circumference and an elevated triglyceride level) as a proxy indicator of visceral fat.^13–15     

Efficacy of pain control with topical lidocaine–epinephrine–tetracaine during laceration repair with tissue adhesive in children: a randomized controlled trial

Background:

Some children feel pain during wound closures using tissue adhesives. We sought to determine whether a topically applied analgesic solution of lidocaine–epinephrine–tetracaine would decrease pain during tissue adhesive repair.

Methods:

We conducted a randomized, placebo-controlled, blinded trial involving 221 children between the ages of 3 months and 17 years. Patients were enrolled between March 2011 and January 2012 when presenting to a tertiary-care pediatric emergency department with lacerations requiring closure with tissue adhesive. Patients received either lidocaine–epinephrine–tetracaine or placebo before undergoing wound closure. Our primary outcome was the pain rating of adhesive application according to the colour Visual Analogue Scale and the Faces Pain Scale — Revised. Our secondary outcomes were physician ratings of difficulty of wound closure and wound hemostasis, in addition to their prediction as to which treatment the patient had received.

Results:

Children who received the analgesic before wound closure reported less pain (median 0.5, interquartile range [IQR] 0.25–1.50) than those who received placebo (median 1.00, IQR 0.38–2.50) as rated using the colour Visual Analogue Scale (p = 0.01) and Faces Pain Scale – Revised (median 0.00, IQR 0.00–2.00, for analgesic v. median 2.00, IQR 0.00–4.00, for placebo, p < 0.01). Patients who received the analgesic were significantly more likely to report having or to appear to have a pain-free procedure (relative risk [RR] of pain 0.54, 95% confidence interval [CI] 0.37–0.80). Complete hemostasis of the wound was also more common among patients who received lidocaine–epinephrine–tetracaine than among those who received placebo (78.2% v. 59.3%, p = 0.008).

Interpretation:

Treating minor lacerations with lidocaine–epinephrine–tetracaine before wound closure with tissue adhesive reduced ratings of pain and increased the proportion of pain-free repairs among children aged 3 months to 17 years. This low-risk intervention may benefit children with lacerations requiring tissue adhesives instead of sutures. Trial registration: ClinicalTrials.gov, no. PR 6138378804.Minor laceration repair with tissue adhesive, or “skin glue,” is common in pediatrics. Although less painful than cutaneous sutures,¹ tissue adhesives polymerize through an exothermic reaction that may cause a burning, painful sensation. Pain is dependent on the specific formulation of the adhesive used and the method of application. One study of different tissue adhesives reported 23.8%–40.5% of participants feeling a “burning sensation”,² whereas another study reported “pain” in 17.6%–44.1% of children.³ The amounts of adhesive applied, method of application and individual patient characteristics can also influence the feeling of pain.^3,4 Because tissue adhesives polymerize on contact with moisture,^4,5 poor wound hemostasis has the potential to cause premature setting of the adhesive, leading to less efficient and more painful repairs.⁶Preventing procedural pain is a high priority in pediatric care.⁷ Inadequate analgesia for pediatric procedures may result in more complicated procedures, increased pain sensitivity with future procedures⁸ and increased fear and anxiety of medical experiences persisting into adulthood.⁹ A practical method to prevent pain during laceration repairs with tissue adhesive would have a substantial benefit for children.A topically applied analgesic solution containing lidocaine–epinephrine–tetracaine with vasoconstrictive properties provides safe and effective pain control during wound repair using sutures.¹⁰ A survey of pediatric emergency fellowship directors in the United States reported that 76% of respondents use this solution or a similar solution when suturing 3-cm chin lacerations in toddlers.¹¹ However, in a hospital chart review, this solution was used in less than half of tissue adhesive repairs, the remainder receiving either local injection of anesthetic or no pain control.¹² Reluctance to use lidocaine–epinephrine–tetracaine with tissue adhesive may be due to the perception that it is not worth the minimum 20-minute wait required for the analgesic to take effect¹³ or to a lack of awareness that tissue adhesives can cause pain.We sought to investigate whether preapplying lidocaine–epinephrine–tetracaine would decrease pain in children during minor laceration repair using tissue adhesive.     

Chronic inflammation as a determinant of future aging phenotypes

Background:

The importance of chronic inflammation as a determinant of aging phenotypes may have been underestimated in previous studies that used a single measurement of inflammatory markers. We assessed inflammatory markers twice over a 5-year exposure period to examine the association between chronic inflammation and future aging phenotypes in a large population of men and women.

Methods:

We obtained data for 3044 middle-aged adults (28.2% women) who were participating in the Whitehall II study and had no history of stroke, myocardial infarction or cancer at our study’s baseline (1997–1999). Interleukin-6 was measured at baseline and 5 years earlier. Cause-specific mortality, chronic disease and functioning were ascertained from hospital data, register linkage and clinical examinations. We used these data to create 4 aging phenotypes at the 10-year follow-up (2007–2009): successful aging (free of major chronic disease and with optimal physical, mental and cognitive functioning), incident fatal or nonfatal cardiovascular disease, death from noncardiovascular causes and normal aging (all other participants).

Results:

Of the 3044 participants, 721 (23.7%) met the criteria for successful aging at the 10-year follow-up, 321 (10.6%) had cardiovascular disease events, 147 (4.8%) died from noncardiovascular causes, and the remaining 1855 (60.9%) were included in the normal aging phenotype. After adjustment for potential confounders, having a high interleukin-6 level (> 2.0 ng/L) twice over the 5-year exposure period nearly halved the odds of successful aging at the 10-year follow-up (odds ratio [OR] 0.53, 95% confidence interval [CI] 0.38–0.74) and increased the risk of future cardiovascular events (OR 1.64, 95% CI 1.15–2.33) and noncardiovascular death (OR 2.43, 95% CI 1.58–3.80).

Interpretation:

Chronic inflammation, as ascertained by repeat measurements, was associated with a range of unhealthy aging phenotypes and a decreased likelihood of successful aging. Our results suggest that assessing long-term chronic inflammation by repeat measurement of interleukin-6 has the potential to guide clinical practice. Chronic inflammation has been implicated in the pathogenesis of age-related conditions, ¹ such as type 2 diabetes, ^{2 , 3} cardiovascular disease, ⁴ cognitive impairment ⁵ and brain atrophy. ⁶ Chronic inflammation may result from or be a cause of age-related disease processes (illustrated in Appendix 1, available at www.cmaj.ca/lookup/suppl/doi:10.1503/cmaj.122072/-/DC1 ). For example, obesity increases inflammation, and chronic inflammation, in turn, contributes to the development of type 2 diabetes by inducing insulin resistance, ^{7 , 8} and to coronary artery disease by promoting atherogenesis. ⁹ Thus, raised levels of inflammation appear to be implicated in various pathological processes leading to diseases in older age. Of the various markers of systemic inflammation, interleukin-6 is particularly relevant to aging outcomes. There is increasing evidence that interleukin-6 is the pro-inflammatory cytokine that “drives” downstream inflammatory markers, such as C-reactive protein and fibrinogen. ^{10 , 11} Interleukin-6, in contrast to C-reactive protein and fibrinogen, is also likely to play a causal role in aging owing to its direct effects on the brain and skeletal muscles. ^{12 , 13} In addition, results of Mendelian randomization studies of interleukin-6 and studies of antagonists are consistent with a causal role for interleukin-6 in relation to coronary artery disease, again in contrast to C-reactive protein and fibrinogen. ¹⁴ However, current understanding of the link between chronic inflammation and aging phenotypes is hampered by the methodologic limitations of many existing studies. Most studies reported an assessment of inflammation based on a single measurement, precluding a distinction between the short-term (acute) and longer-term (chronic) impact of the inflammatory process on disease outcomes. ⁷ We conducted a study using 2 measurements of interleukin-6 obtained about 5 years apart to examine the association between chronic inflammation and aging phenotypes assessed 10 years later in a large population of men and women. Because inflammation characterizes a wide range of pathological processes, we considered several aging phenotypes, including cardiovascular disease (fatal and nonfatal), death from noncardiovascular causes and successful aging (optimal functioning across different physical, mental and cognitive domains).     

Prevalence of and factors associated with head impact during falls in older adults in long-term care

Background:

Falls cause more than 60% of head injuries in older adults. Lack of objective evidence on the circumstances of these events is a barrier to prevention. We analyzed video footage to determine the frequency of and risk factors for head impact during falls in older adults in 2 long-term care facilities.

Methods:

Over 39 months, we captured on video 227 falls involving 133 residents. We used a validated questionnaire to analyze the mechanisms of each fall. We then examined whether the probability for head impact was associated with upper-limb protective responses (hand impact) and fall direction.

Results:

Head impact occurred in 37% of falls, usually onto a vinyl or linoleum floor. Hand impact occurred in 74% of falls but had no significant effect on the probability of head impact (p = 0.3). An increased probability of head impact was associated with a forward initial fall direction, compared with backward falls (odds ratio [OR] 2.7, 95% confidence interval [CI] 1.3–5.9) or sideways falls (OR 2.8, 95% CI 1.2–6.3). In 36% of sideways falls, residents rotated to land backwards, which reduced the probability of head impact (OR 0.2, 95% CI 0.04–0.8).

Interpretation:

Head impact was common in observed falls in older adults living in long-term care facilities, particularly in forward falls. Backward rotation during descent appeared to be protective, but hand impact was not. Attention to upper-limb strength and teaching rotational falling techniques (as in martial arts training) may reduce fall-related head injuries in older adults.Falls from standing height or lower are the cause of more than 60% of hospital admissions for traumatic brain injury in adults older than 65 years.^1–5 Traumatic brain injury accounts for 32% of hospital admissions and more than 50% of deaths from falls in older adults.^1,6–8 Furthermore, the incidence and age-adjusted rate of fall-related traumatic brain injury is increasing,^1,9 especially among people older than 80 years, among whom rates have increased threefold over the past 30 years.¹⁰ One-quarter of fall-related traumatic brain injuries in older adults occur in long-term care facilities.¹The development of improved strategies to prevent fall-related traumatic brain injuries is an important but challenging task. About 60% of residents in long-term care facilities fall at least once per year,¹¹ and falls result from complex interactions of physiologic, environmental and situational factors.^12–16 Any fall from standing height has sufficient energy to cause brain injury if direct impact occurs between the head and a rigid floor surface.^17–19 Improved understanding is needed of the factors that separate falls that result in head impact and injury from those that do not.^1,10 Falls in young adults rarely result in head impact, owing to protective responses such as use of the upper limbs to stop the fall, trunk flexion and rotation during descent.^20–23 We have limited evidence of the efficacy of protective responses to falls among older adults.In the current study, we analyzed video footage of real-life falls among older adults to estimate the prevalence of head impact from falls, and to examine the association between head impact, and biomechanical and situational factors.     

Effects of daily iron supplementation in primary-school–aged children: systematic review and meta-analysis of randomized controlled trials

Background:

Anemia is an important public health and clinical problem. Observational studies have linked iron deficiency and anemia in children with many poor outcomes, including impaired cognitive development; however, iron supplementation, a widely used preventive and therapeutic strategy, is associated with adverse effects. Primary-school–aged children are at a critical stage in intellectual development, and optimization of their cognitive performance could have long-lasting individual and population benefits. In this study, we summarize the evidence for the benefits and safety of daily iron supplementation in primary-school–aged children.

Methods:

We searched electronic databases (including MEDLINE and Embase) and other sources (July 2013) for randomized and quasi-randomized controlled trials involving daily iron supplementation in children aged 5–12 years. We combined the data using random effects meta-analysis.

Results:

We identified 16 501 studies; of these, we evaluated 76 full-text papers and included 32 studies including 7089 children. Of the included studies, 31 were conducted in low- or middle-income settings. Iron supplementation improved global cognitive scores (standardized mean difference 0.50, 95% confidence interval [CI] 0.11 to 0.90, p = 0.01), intelligence quotient among anemic children (mean difference 4.55, 95% CI 0.16 to 8.94, p = 0.04) and measures of attention and concentration. Iron supplementation also improved age-adjusted height among all children and age-adjusted weight among anemic children. Iron supplementation reduced the risk of anemia by 50% and the risk of iron deficiency by 79%. Adherence in the trial settings was generally high. Safety data were limited.

Interpretation:

Our analysis suggests that iron supplementation safely improves hematologic and nonhematologic outcomes among primary-school–aged children in low- or middle-income settings and is well-tolerated.An estimated 25% of school-aged children worldwide are anemic.¹ Iron deficiency is thought to account for about half of the global cases of anemia² and is associated with inadequate dietary iron and, in developing settings, hookworm and schistosomiasis.³ In developed settings, anemia is prevalent among disadvantaged populations, including newly arrived refugees, indigenous people⁴ and some ethnic groups (e.g., Hispanic people in the United States).^5,6 About 3% of primary-school–aged children in Canada are anemic.⁷ Programs to address anemia are constrained by concerns that iron supplements cause adverse effects, including an increased risk of infections such as malaria in endemic areas.⁸In observational studies, iron deficiency has been associated with impaired cognitive and physical development. It has been estimated that each 10 g/L decrement in hemoglobin reduces future intelligence quotient (IQ) by 1.73 points.⁹ However, observational data are susceptible to confounding,¹⁰ and a causal relation between iron deficiency and cognitive impairment has not been confirmed.¹¹ Randomized controlled trials should overcome confounding, but results of trials examining this question have not agreed.Optimizing cognitive and physical development in primary-school–aged children could have life-long benefits.¹² However, anemia-control recommendations must balance safety and efficacy. We performed a systematic review of the effects of daily iron supplementation, a commonly used strategy to combat anemia,² in primary-school–aged children. We examined cognitive, growth and hematologic outcomes and adverse effects across all settings.     

Rates of hemorrhage during warfarin therapy for atrial fibrillation

Background:

Although warfarin has been extensively studied in clinical trials, little is known about rates of hemorrhage attributable to its use in routine clinical practice. Our objective was to examine incident hemorrhagic events in a large population-based cohort of patients with atrial fibrillation who were starting treatment with warfarin.

Methods:

We conducted a population-based cohort study involving residents of Ontario (age ≥ 66 yr) with atrial fibrillation who started taking warfarin between Apr. 1, 1997, and Mar. 31, 2008. We defined a major hemorrhage as any visit to hospital for hemorrage. We determined crude rates of hemorrhage during warfarin treatment, overall and stratified by CHADS₂ score (congestive heart failure, hypertension, age ≥ 75 yr, diabetes mellitus and prior stroke, transient ischemic attack or thromboembolism).

Results:

We included 125 195 patients with atrial fibrillation who started treatment with warfarin during the study period. Overall, the rate of hemorrhage was 3.8% (95% confidence interval [CI] 3.8%–3.9%) per person-year. The risk of major hemorrhage was highest during the first 30 days of treatment. During this period, rates of hemorrhage were 11.8% (95% CI 11.1%–12.5%) per person-year in all patients and 16.7% (95% CI 14.3%–19.4%) per person-year among patients with a CHADS₂ scores of 4 or greater. Over the 5-year follow-up, 10 840 patients (8.7%) visited the hospital for hemorrhage; of these patients, 1963 (18.1%) died in hospital or within 7 days of being discharged.

Interpretation:

In this large cohort of older patients with atrial fibrillation, we found that rates of hemorrhage are highest within the first 30 days of warfarin therapy. These rates are considerably higher than the rates of 1%–3% reported in randomized controlled trials of warfarin therapy. Our study provides timely estimates of warfarin-related adverse events that may be useful to clinicians, patients and policy-makers as new options for treatment become available.Atrial fibrillation is a major risk factor for stroke and systemic embolism, and strong evidence supports the use of the anticoagulant warfarin to reduce this risk.^1–3 However, warfarin has a narrow therapeutic range and requires regular monitoring of the international normalized ratio to optimize its effectiveness and minimize the risk of hemorrhage.^4,5 Although rates of major hemorrhage reported in trials of warfarin therapy typically range between 1% and 3% per person-year,^6–11 observational studies suggest that rates may be considerably higher when warfarin is prescribed outside of a clinical trial setting,^12–15 approaching 7% per person-year in some studies.^13–15 The different safety profiles derived from clinical trials and observational data may reflect the careful selection of patients, precise definitions of bleeding and close monitoring in the trial setting. Furthermore, although a few observational studies suggest that hemorrhage rates are higher than generally appreciated, these studies involve small numbers of patients who received care in specialized settings.^14–16 Consequently, the generalizability of their results to general practice may be limited.More information regarding hemorrhage rates during warfarin therapy is particularly important in light of the recent introduction of new oral anticoagulant agents such as dabigatran, rivaroxaban and apixaban, which may be associated with different outcome profiles.^17–19 There are currently no large studies offering real-world, population-based estimates of hemorrhage rates among patients taking warfarin, which are needed for future comparisons with new anticoagulant agents once they are widely used in routine clinical practice.²⁰We sought to describe the risk of incident hemorrhage in a large population-based cohort of patients with atrial fibrillation who had recently started warfarin therapy.