Gut microbiota of healthy Canadian infants: profiles by mode of delivery and infant diet at 4 months

Background:

The gut microbiota is essential to human health throughout life, yet the acquisition and development of this microbial community during infancy remains poorly understood. Meanwhile, there is increasing concern over rising rates of cesarean delivery and insufficient exclusive breastfeeding of infants in developed countries. In this article, we characterize the gut microbiota of healthy Canadian infants and describe the influence of cesarean delivery and formula feeding.

Methods:

We included a subset of 24 term infants from the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort. Mode of delivery was obtained from medical records, and mothers were asked to report on infant diet and medication use. Fecal samples were collected at 4 months of age, and we characterized the microbiota composition using high-throughput DNA sequencing.

Results:

We observed high variability in the profiles of fecal microbiota among the infants. The profiles were generally dominated by Actinobacteria (mainly the genus Bifidobacterium) and Firmicutes (with diverse representation from numerous genera). Compared with breastfed infants, formula-fed infants had increased richness of species, with overrepresentation of Clostridium difficile. Escherichia–Shigella and Bacteroides species were underrepresented in infants born by cesarean delivery. Infants born by elective cesarean delivery had particularly low bacterial richness and diversity.

Interpretation:

These findings advance our understanding of the gut microbiota in healthy infants. They also provide new evidence for the effects of delivery mode and infant diet as determinants of this essential microbial community in early life.The human body harbours trillions of microbes, known collectively as the “human microbiome.” By far the highest density of commensal bacteria is found in the digestive tract, where resident microbes outnumber host cells by at least 10 to 1. Gut bacteria play a fundamental role in human health by promoting intestinal homeostasis, stimulating development of the immune system, providing protection against pathogens, and contributing to the processing of nutrients and harvesting of energy.^1,2 The disruption of the gut microbiota has been linked to an increasing number of diseases, including inflammatory bowel disease, necrotizing enterocolitis, diabetes, obesity, cancer, allergies and asthma.¹ Despite this evidence and a growing appreciation for the integral role of the gut microbiota in lifelong health, relatively little is known about the acquisition and development of this complex microbial community during infancy.³Two of the best-studied determinants of the gut microbiota during infancy are mode of delivery and exposure to breast milk.^4,5 Cesarean delivery perturbs normal colonization of the infant gut by preventing exposure to maternal microbes, whereas breastfeeding promotes a “healthy” gut microbiota by providing selective metabolic substrates for beneficial bacteria.^3,5 Despite recommendations from the World Health Organization,⁶ the rate of cesarean delivery has continued to rise in developed countries and rates of breastfeeding decrease substantially within the first few months of life.^7,8 In Canada, more than 1 in 4 newborns are born by cesarean delivery, and less than 15% of infants are exclusively breastfed for the recommended duration of 6 months.^9,10 In some parts of the world, elective cesarean deliveries are performed by maternal request, often because of apprehension about pain during childbirth, and sometimes for patient–physician convenience.¹¹The potential long-term consequences of decisions regarding mode of delivery and infant diet are not to be underestimated. Infants born by cesarean delivery are at increased risk of asthma, obesity and type 1 diabetes,¹² whereas breastfeeding is variably protective against these and other disorders.¹³ These long-term health consequences may be partially attributable to disruption of the gut microbiota.^12,14Historically, the gut microbiota has been studied with the use of culture-based methodologies to examine individual organisms. However, up to 80% of intestinal microbes cannot be grown in culture.^3,15 New technology using culture-independent DNA sequencing enables comprehensive detection of intestinal microbes and permits simultaneous characterization of entire microbial communities. Multinational consortia have been established to characterize the “normal” adult microbiome using these exciting new methods;¹⁶ however, these methods have been underused in infant studies. Because early colonization may have long-lasting effects on health, infant studies are vital.^3,4 Among the few studies of infant gut microbiota using DNA sequencing, most were conducted in restricted populations, such as infants delivered vaginally,¹⁷ infants born by cesarean delivery who were formula-fed¹⁸ or preterm infants with necrotizing enterocolitis.¹⁹Thus, the gut microbiota is essential to human health, yet the acquisition and development of this microbial community during infancy remains poorly understood.³ In the current study, we address this gap in knowledge using new sequencing technology and detailed exposure assessments²⁰ of healthy Canadian infants selected from a national birth cohort to provide representative, comprehensive profiles of gut microbiota according to mode of delivery and infant diet.     

A qualitative investigation of smoke-free policies on hospital property

Background:

Many hospitals have adopted smoke-free policies on their property. We examined the consequences of such polices at two Canadian tertiary acute-care hospitals.

Methods:

We conducted a qualitative study using ethnographic techniques over a six-month period. Participants (n = 186) shared their perspectives on and experiences with tobacco dependence and managing the use of tobacco, as well as their impressions of the smoke-free policy. We interviewed inpatients individually from eight wards (n = 82), key policy-makers (n = 9) and support staff (n = 14) and held 16 focus groups with health care providers and ward staff (n = 81). We also reviewed ward documents relating to tobacco dependence and looked at smoking-related activities on hospital property.

Results:

Noncompliance with the policy and exposure to secondhand smoke were ongoing concerns. Peoples’ impressions of the use of tobacco varied, including divergent opinions as to whether such use was a bad habit or an addiction. Treatment for tobacco dependence and the management of symptoms of withdrawal were offered inconsistently. Participants voiced concerns over patient safety and leaving the ward to smoke.

Interpretation:

Policies mandating smoke-free hospital property have important consequences beyond noncompliance, including concerns over patient safety and disruptions to care. Without adequately available and accessible support for withdrawal from tobacco, patients will continue to face personal risk when they leave hospital property to smoke.Canadian cities and provinces have passed smoking bans with the goal of reducing people’s exposure to secondhand smoke in workplaces, public spaces and on the property adjacent to public buildings.^1,2 In response, Canadian health authorities and hospitals began implementing policies mandating smoke-free hospital property, with the goals of reducing the exposure of workers, patients and visitors to tobacco smoke while delivering a public health message about the dangers of smoking.^2–5 An additional anticipated outcome was the reduced use of tobacco among patients and staff. The impetuses for adopting smoke-free policies include public support for such legislation and the potential for litigation for exposure to second-hand smoke.^2,4Tobacco use is a modifiable risk factor associated with a variety of cancers, cardiovascular diseases and respiratory conditions.^6–11 Patients in hospital who use tobacco tend to have more surgical complications and exacerbations of acute and chronic health conditions than patients who do not use tobacco.^6–11 Any policy aimed at reducing exposure to tobacco in hospitals is well supported by evidence, as is the integration of interventions targetting tobacco dependence.¹² Unfortunately, most of the nearly five million Canadians who smoke will receive suboptimal treatment,¹³ as the routine provision of interventions for tobacco dependence in hospital settings is not a practice norm.^14–16 In smoke-free hospitals, two studies suggest minimal support is offered for withdrawal, ^17,18 and one reports an increased use of nicotine-replacement therapy after the implementation of the smoke-free policy.¹⁹Assessments of the effectiveness of smoke-free policies for hospital property tend to focus on noncompliance and related issues of enforcement.^17,20,21 Although evidence of noncompliance and litter on hospital property^2,17,20 implies ongoing exposure to tobacco smoke, half of the participating hospital sites in one study reported less exposure to tobacco smoke within hospital buildings and on the property.¹⁸ In addition, there is evidence to suggest some decline in smoking among staff.^18,19,21,22We sought to determine the consequences of policies mandating smoke-free hospital property in two Canadian acute-care hospitals by eliciting lived experiences of the people faced with enacting the policies: patients and health care providers. In addition, we elicited stories from hospital support staff and administrators regarding the policies.     

Risk of vascular events in patients with polymyalgia rheumatica

Background:

Polymyalgia rheumatica is one of the most common inflammatory rheumatologic conditions in older adults. Other inflammatory rheumatologic disorders are associated with an excess risk of vascular disease. We investigated whether polymyalgia rheumatica is associated with an increased risk of vascular events.

Methods:

We used the General Practice Research Database to identify patients with a diagnosis of incident polymyalgia rheumatica between Jan. 1, 1987, and Dec. 31, 1999. Patients were matched by age, sex and practice with up to 5 patients without polymyalgia rheumatica. Patients were followed until their first vascular event (cardiovascular, cerebrovascular, peripheral vascular) or the end of available records (May 2011). All participants were free of vascular disease before the diagnosis of polymyalgia rheumatica (or matched date). We used Cox regression models to compare time to first vascular event in patients with and without polymyalgia rheumatica.

Results:

A total of 3249 patients with polymyalgia rheumatica and 12 735 patients without were included in the final sample. Over a median follow-up period of 7.8 (interquartile range 3.3–12.4) years, the rate of vascular events was higher among patients with polymyalgia rheumatica than among those without (36.1 v. 12.2 per 1000 person-years; adjusted hazard ratio 2.6, 95% confidence interval 2.4–2.9). The increased risk of a vascular event was similar for each vascular disease end point. The magnitude of risk was higher in early disease and in patients younger than 60 years at diagnosis.

Interpretation:

Patients with polymyalgia rheumatica have an increased risk of vascular events. This risk is greatest in the youngest age groups. As with other forms of inflammatory arthritis, patients with polymyalgia rheumatica should have their vascular risk factors identified and actively managed to reduce this excess risk.Inflammatory rheumatologic disorders such as rheumatoid arthritis,^1,2 systemic lupus erythematosus,^2,3 gout,⁴ psoriatic arthritis^2,5 and ankylosing spondylitis^2,6 are associated with an increased risk of vascular disease, especially cardiovascular disease, leading to substantial morbidity and premature death.^2–6 Recognition of this excess vascular risk has led to management guidelines advocating screening for and management of vascular risk factors.^7–9Polymyalgia rheumatica is one of the most common inflammatory rheumatologic conditions in older adults,¹⁰ with a lifetime risk of 2.4% for women and 1.7% for men.¹¹ To date, evidence regarding the risk of vascular disease in patients with polymyalgia rheumatica is unclear. There are a number of biologically plausible mechanisms between polymyalgia rheumatica and vascular disease. These include the inflammatory burden of the disease,^12,13 the association of the disease with giant cell arteritis (causing an inflammatory vasculopathy, which may lead to subclinical arteritis, stenosis or aneurysms),¹⁴ and the adverse effects of long-term corticosteroid treatment (e.g., diabetes, hypertension and dyslipidemia).^15,16 Paradoxically, however, use of corticosteroids in patients with polymyalgia rheumatica may actually decrease vascular risk by controlling inflammation.¹⁷ A recent systematic review concluded that although some evidence exists to support an association between vascular disease and polymyalgia rheumatica,¹⁸ the existing literature presents conflicting results, with some studies reporting an excess risk of vascular disease^19,20 and vascular death,^21,22 and others reporting no association.^23–26 Most current studies are limited by poor methodologic quality and small samples, and are based on secondary care cohorts, who may have more severe disease, yet most patients with polymyalgia rheumatica receive treatment exclusively in primary care.²⁷The General Practice Research Database (GPRD), based in the United Kingdom, is a large electronic system for primary care records. It has been used as a data source for previous studies,²⁸ including studies on the association of inflammatory conditions with vascular disease²⁹ and on the epidemiology of polymyalgia rheumatica in the UK.³⁰ The aim of the current study was to examine the association between polymyalgia rheumatica and vascular disease in a primary care population.     

Association between hypertensive disorders during pregnancy and end-stage renal disease: a population-based study

Background:

Studies into the association between hypertensive disorders during pregnancy and end-stage renal disease are limited. We investigated the risk of end-stage renal disease after delivery among women with hypertensive disorders during pregnancy.

Methods:

We used insurance claims data from 1998 to 2009 to identify 26 651 women aged 19–40 years old who experienced hypertensive disorders during pregnancy; these women had no history of hypertension, diabetes, kidney disease or lupus. We also randomly selected 213 397 women without hypertensive disorders during pregnancy as a comparison cohort; the frequency was matched by age and index year of pregnancy. We compared the incidence of end-stage renal disease in the 2 cohorts. We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) after controlling for demographic and clinical factors.

Results:

Women with hypertensive disorders during pregnancy had a greater risk of chronic kidney disease and end-stage renal disease, with adjusted HRs of 9.38 (95% CI 7.09–12.4) and 12.4 (95% CI 8.54–18.0), respectively, after controlling for urban status, coronary artery disease, congestive heart failure, hyperlipidemia and abruption. The HR for end-stage renal disease was 2.72 (95% CI 1.76–4.22) after we also controlled for hypertension and diabetes. Women with preeclampsia or eclampsia had a higher risk of end-stage renal disease (adjusted HR 14.0, 95% CI 9.43–20.7) than women who had gestational hypertension only (adjusted HR 9.03, 95% CI 5.20–15.7).

Interpretation:

Women with hypertensive disorders during pregnancy were at a high risk of end-stage renal disease. The risk was much greater for women who had preeclampsia or eclampsia than those who had gestational hypertension only.Hypertensive disorders during pregnancy are major causes of maternal and fetal morbidity and mortality, affecting 5%–10% of pregnancies.^1,2 Hypertensive disorders during pregnancy include gestational hypertension and preeclampsia.³ Gestational hypertension is referred to as new-onset hypertension (blood pressure > 140/90 mm Hg) without proteinuria after 20-weeks’ gestation.³ Preeclampsia is characterized by new-onset hypertension (blood pressure > 140/90 mm Hg) with proteinuria of at least 300 mg in a 24-hour urine sample after 20-weeks’ gestation.³ Gestational hypertension progresses to preeclampsia in 10%–20% of pregnant women.⁴ The risk factors associated with preeclampsia include family history of preeclampsia, first pregnancy, multiple gestation, advanced maternal age, obesity, pre-existing hypertension, renal disease and diabetes mellitus.⁵ Women with a history of hypertensive disorders during pregnancy are at higher risk of hypertension, diabetes mellitus and cardiovascular disease in later life. Hypertensive disorders during pregnancy and cardiovascular disease share several common risk factors, such as obesity, pre-existing hypertension, renal disease and insulin resistance.^6–14 Hypertensive disorders during pregnancy also increase the risk of cardiovascular disease because of long-term metabolic and vascular changes.¹⁵Hypertensive disorders during pregnancy affect the function and morphology of the kidney.¹⁶ Previous studies have reported an increased prevalence of microalbuminuria after pregnancy in women who had a hypertensive disorder during pregnancy.^17,18 In a case–control study, there was an association between biopsy-proven renal disease and a history of preeclampsia.¹⁹ However, studies about whether hypertensive disorders during pregnancy are associated with end-stage renal disease in later life are limited.²⁰ Only 1 study, performed using birth and renal registries from Norway, has reported that women with preeclampsia during their first pregnancy had a 3.2-fold higher risk of end-stage renal disease.²⁰ In the present study, we investigated the risk of end-stage renal disease among Taiwanese women who had a hypertensive disorder during pregnancy.     

Risk of bleeding associated with combined use of selective serotonin reuptake inhibitors and antiplatelet therapy following acute myocardial infarction

Background:

Patients prescribed antiplatelet treatment to prevent recurrent acute myocardial infarction are often also given a selective serotonin reuptake inhibitor (SSRI) to treat coexisting depression. Use of either treatment may increase the risk of bleeding. We assessed the risk of bleeding among patients taking both medications following acute myocardial infarction.

Methods:

We conducted a retrospective cohort study using hospital discharge abstracts, physician billing information, medication reimbursement claims and demographic data from provincial health services administrative databases. We included patients 50 years of age or older who were discharged from hospital with antiplatelet therapy following acute myocardial infarction between January 1998 and March 2007. Patients were followed until admission to hospital due to a bleeding episode, admission to hospital due to recurrent acute myocardial infarction, death or the end of the study period.

Results:

The 27 058 patients in the cohort received the following medications at discharge: acetylsalicylic acid (ASA) (n = 14 426); clopidogrel (n = 2467), ASA and clopidogrel (n = 9475); ASA and an SSRI (n = 406); ASA, clopidogrel and an SSRI (n = 239); or clopidogrel and an SSRI (n = 45). Compared with ASA use alone, the combined use of an SSRI with antiplatelet therapy was associated with an increased risk of bleeding (ASA and SSRI: hazard ratio [HR] 1.42, 95% confidence interval [CI] 1.08–1.87; ASA, clopidogrel and SSRI: HR 2.35, 95% CI 1.61–3.42). Compared with dual antiplatelet therapy alone (ASA and clopidogrel), combined use of an SSRI and dual antiplatelet therapy was associated with an increased risk of bleeding (HR 1.57, 95% CI 1.07–2.32).

Interpretation:

Patients taking an SSRI together with ASA or dual antiplatelet therapy following acute myocardial infarction were at increased risk of bleeding.Antiplatelet agents such as acetylsalicylic acid (ASA) and clopidogrel are a mainstay of therapy following acute myocardial infarction. These agents are effective in reducing the risk of recurrent acute myocardial infarction and other cardiovascular events, with the potential for additive benefit when used in combination.^1–3 The risk of bleeding associated with their use, however, is of concern.^4–6 This risk may be increased further by the frequent concomitant use of other medications associated with an increased risk of bleeding, such as anticoagulant therapy⁷ and selective serotonin reuptake inhibitors (SSRIs).Up to 20% of patients with cardiovascular disease experience depression and are most often prescribed an SSRI.^8–13 The vast majority of these patients also use antiplatelet therapy. The risk of bleeding associated with combining SSRI therapy with single or dual antiplatelet therapy is uncertain. Two large clinical trials that examined SSRI use following acute myocardial infarction did not specifically report on the risk of bleeding,^14,15 and earlier studies suggested no increase in risk associated with SSRI therapy combined with single-agent antiplatelet therapy.^16,17SSRI use itself has been associated with an increased risk of bleeding, particularly during the first month of use.¹⁸ The inhibition of serotonin transporters by SSRIs is thought to be responsible for the risk of bleeding.¹⁹ Platelets release serotonin at sites of bleeding and vascular damage; however, they do not synthesize serotonin and instead acquire it from the blood and store it.^19,20 By this mechanism, SSRIs may also worsen the bleeding caused by ASA and clopidogrel.^19,20 Inhibition of cytochrome P450 by certain SSRIs has also been associated with increased risk of drug interaction causing bleeding;²¹ however, data on this issue are scarce.We examined the risk of bleeding associated with the use of SSRIs when combined with single and dual antiplatelet therapy among patients following acute myocardial infarction.     

Secular trends in acute dialysis after elective major surgery �� 1995 to 2009

Background:

Acute kidney injury is a serious complication of elective major surgery. Acute dialysis is used to support life in the most severe cases. We examined whether rates and outcomes of acute dialysis after elective major surgery have changed over time.

Methods:

We used data from Ontario’s universal health care databases to study all consecutive patients who had elective major surgery at 118 hospitals between 1995 and 2009. Our primary outcomes were acute dialysis within 14 days of surgery, death within 90 days of surgery and chronic dialysis for patients who did not recover kidney function.

Results:

A total of 552 672 patients underwent elective major surgery during the study period, 2231 of whom received acute dialysis. The incidence of acute dialysis increased steadily from 0.2% in 1995 (95% confidence interval [CI] 0.15–0.2) to 0.6% in 2009 (95% CI 0.6–0.7). This increase was primarily in cardiac and vascular surgeries. Among patients who received acute dialysis, 937 died within 90 days of surgery (42.0%, 95% CI 40.0–44.1), with no change in 90-day survival over time. Among the 1294 patients who received acute dialysis and survived beyond 90 days, 352 required chronic dialysis (27.2%, 95% CI 24.8–29.7), with no change over time.

Interpretation:

The use of acute dialysis after cardiac and vascular surgery has increased substantially since 1995. Studies focusing on interventions to better prevent and treat perioperative acute kidney injury are needed.More than 230 million elective major surgeries are done annually worldwide.¹ Acute kidney injury is a serious complication of major surgery. It represents a sudden loss of kidney function that affects morbidity, mortality and health care costs.² Dialysis is used for the most severe forms of acute kidney injury. In the nonsurgical setting, the incidence of acute dialysis has steadily increased over the last 15 years, and patients are now more likely to survive to discharge from hospital.^3–5 Similarly, in the surgical setting, the incidence of acute dialysis appears to be increasing over time,^6–10 with declining inhospital mortality.^8,10,11Although previous studies have improved our understanding of the epidemiology of acute dialysis in the surgical setting, several questions remain. Many previous studies were conducted at a single centre, thereby limiting their generalizability.^6,12–14 Most multicentre studies were conducted in the nonsurgical setting and used diagnostic codes for acute kidney injury not requiring dialysis; however, these codes can be inaccurate.^15,16 In contrast, a procedure such as dialysis is easily determined. The incidence of acute dialysis after elective surgery is of particular interest given the need for surgical consent, the severe nature of the event and the potential for mitigation. The need for chronic dialysis among patients who do not recover renal function after surgery has been poorly studied, yet this condition has a major affect on patient survival and quality of life.¹⁷ For these reasons, we studied secular trends in acute dialysis after elective major surgery, focusing on incidence, 90-day mortality and need for chronic dialysis.     

Mediterranean diets and metabolic syndrome status in the PREDIMED randomized trial

Background:

Little evidence exists on the effect of an energy-unrestricted healthy diet on metabolic syndrome. We evaluated the long-term effect of Mediterranean diets ad libitum on the incidence or reversion of metabolic syndrome.

Methods:

We performed a secondary analysis of the PREDIMED trial — a multicentre, randomized trial done between October 2003 and December 2010 that involved men and women (age 55–80 yr) at high risk for cardiovascular disease. Participants were randomly assigned to 1 of 3 dietary interventions: a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with nuts or advice on following a low-fat diet (the control group). The interventions did not include increased physical activity or weight loss as a goal. We analyzed available data from 5801 participants. We determined the effect of diet on incidence and reversion of metabolic syndrome using Cox regression analysis to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).

Results:

Over 4.8 years of follow-up, metabolic syndrome developed in 960 (50.0%) of the 1919 participants who did not have the condition at baseline. The risk of developing metabolic syndrome did not differ between participants assigned to the control diet and those assigned to either of the Mediterranean diets (control v. olive oil HR 1.10, 95% CI 0.94–1.30, p = 0.231; control v. nuts HR 1.08, 95% CI 0.92–1.27, p = 0.3). Reversion occurred in 958 (28.2%) of the 3392 participants who had metabolic syndrome at baseline. Compared with the control group, participants on either Mediterranean diet were more likely to undergo reversion (control v. olive oil HR 1.35, 95% CI 1.15–1.58, p < 0.001; control v. nuts HR 1.28, 95% CI 1.08–1.51, p < 0.001). Participants in the group receiving olive oil supplementation showed significant decreases in both central obesity and high fasting glucose (p = 0.02); participants in the group supplemented with nuts showed a significant decrease in central obesity.

Interpretation:

A Mediterranean diet supplemented with either extra virgin olive oil or nuts is not associated with the onset of metabolic syndrome, but such diets are more likely to cause reversion of the condition. An energy-unrestricted Mediterranean diet may be useful in reducing the risks of central obesity and hyperglycemia in people at high risk of cardiovascular disease. Trial registration: ClinicalTrials.gov, no. ISRCTN35739639.Metabolic syndrome is a cluster of 3 or more related cardiometabolic risk factors: central obesity (determined by waist circumference), hypertension, hypertriglyceridemia, low plasma high-density lipoprotein (HDL) cholesterol levels and hyperglycemia. Having the syndrome increases a person’s risk for type 2 diabetes and cardiovascular disease.^1,2 In addition, the condition is associated with increased morbidity and all-cause mortality.^1,3–5 The worldwide prevalence of metabolic syndrome in adults approaches 25%^6–8 and increases with age,⁷ especially among women,^8,9 making it an important public health issue.Several studies have shown that lifestyle modifications,¹⁰ such as increased physical activity,¹¹ adherence to a healthy diet^12,13 or weight loss,^14–16 are associated with reversion of the metabolic syndrome and its components. However, little information exists as to whether changes in the overall dietary pattern without weight loss might also be effective in preventing and managing the condition.The Mediterranean diet is recognized as one of the healthiest dietary patterns. It has shown benefits in patients with cardiovascular disease^17,18 and in the prevention and treatment of related conditions, such as diabetes,^19–21 hypertension^22,23 and metabolic syndrome.²⁴Several cross-sectional^25–29 and prospective^30–32 epidemiologic studies have suggested an inverse association between adherence to the Mediterranean diet and the prevalence or incidence of metabolic syndrome. Evidence from clinical trials has shown that an energy-restricted Mediterranean diet³³ or adopting a Mediterranean diet after weight loss³⁴ has a beneficial effect on metabolic syndrome. However, these studies did not determine whether the effect could be attributed to the weight loss or to the diets themselves.Seminal data from the PREDIMED (PREvención con DIeta MEDiterránea) study suggested that adherence to a Mediterranean diet supplemented with nuts reversed metabolic syndrome more so than advice to follow a low-fat diet.³⁵ However, the report was based on data from only 1224 participants followed for 1 year. We have analyzed the data from the final PREDIMED cohort after a median follow-up of 4.8 years to determine the long-term effects of a Mediterranean diet on metabolic syndrome.     

Involving patients in cardiovascular risk management with nurse-led clinics: a cluster randomized controlled trial

Background

Preventive guidelines on cardiovascular risk management recommend lifestyle changes. Support for lifestyle changes may be a useful task for practice nurses, but the effect of such interventions in primary prevention is not clear. We examined the effect of involving patients in nurse-led cardiovascular risk management on lifestyle adherence and cardiovascular risk.

Methods

We performed a cluster randomized controlled trial in 25 practices that included 615 patients. The intervention consisted of nurse-led cardiovascular risk management, including risk assessment, risk communication, a decision aid and adapted motivational interviewing. The control group received a minimal nurse-led intervention. The self-reported outcome measures at one year were smoking, alcohol use, diet and physical activity. Nurses assessed 10-year cardiovascular mortality risk after one year.

Results

There were no significant differences between the intervention groups. The effect of the intervention on the consumption of vegetables and physical activity was small, and some differences were only significant for subgroups. The effects of the intervention on the intake of fat, fruit and alcohol and smoking were not significant. We found no effect between the groups for cardiovascular 10-year risk.

Interpretation

Nurse-led risk communication, use of a decision aid and adapted motivational interviewing did not lead to relevant differences between the groups in terms of lifestyle changes or cardiovascular risk, despite significant within-group differences.It is not clear if programs for lifestyle change are effective in the primary prevention of cardiovascular diseases. Some studies have shown lifestyle improvements with cardiovascular rehabilitation programs,^1–3 and studies in primary prevention have suggested small, but potentially important, reductions in the risk of cardiovascular disease. However, these studies have had limitations and have recommended further research.^4,5 According to national and international guidelines for cardiovascular risk management, measures to prevent cardiovascular disease, such as patient education and support for lifestyle change, can be delegated to practice nurses in primary care.^6–8 However, we do not know whether the delivery of primary prevention programs by practice nurses is effective. We also do no know the effect of nurse-led prevention, including shared decision-making and risk communication, on cardiovascular risk.Because an unhealthy lifestyle plays an important role in the development of cardiovascular disease,^9,10 preventive guidelines on cardiovascular disease and diabetes recommend education and counselling about smoking, diet, physical exercise and alcohol consumption for patients with moderately and highly increased risk.^6,11 These patients are usually monitored in primary care practices. The adherence to lifestyle advice ranges from 20% to 90%,^12–15 and improving adherence requires effective interventions, comprising cognitive, behavioural and affective components (strategies to influence adherence to lifestyle advice via feelings and emotions or social relationships and social supports).¹⁶ Shared treatment decisions are highly preferred. Informed and shared decision-making requires that all information about the cardiovascular risk and the pros and cons of the risk-reduction options be shared with the patient, and that the patients’ individual values, personal resources and capacity for self-determination be respected.^17–19 In our cardiovascular risk reduction study,²⁰ we developed an innovative implementation strategy that included a central role for practice nurses. Key elements of our intervention included risk assessment, risk communication, use of a decision aid and adapted motivational interviewing (Box 1).^19,21,22

Box 1.?Key features of the nurse-led intervention

• Risk assessment (intervention and control): The absolute 10-year mortality risk from cardiovascular diseases was assessed with use of a risk table from the Dutch guidelines (for patients without diabetes) or the UK Prospective Diabetes Study risk engine (for patients with diabetes).^6,23 Nurses in the control group continued to provide usual care after this step.
• Risk communication (intervention only): Nurses informed the patients of their absolute 10-year cardiovascular mortality risk using a risk communication tool developed for this study.^24–37
• Decision support (intervention only): Nurses provied support to the patients using an updated decision aid.²⁸ This tool facilitated the nurses’ interaction with the patients to arrive at informed, value-based choices for risk reduction. The tool provided information about the options and their associated relevant outcomes.
• Adapted motivational interviewing (intervention only): Nurses discussed the options for risk reduction. The patient’s personal values were elicited using adapted motivational interviewing.

In the present study, we investigated whether a nurse-led intervention in primary care had a positive effect on lifestyle and 10-year cardiovascular risk. We hypothesized that involving patients in decision-making would increase adherence to lifestyle changes and decrease the absolute risk of 10-year cardiovascular mortality.     

Effect of ambient air pollution on the incidence of appendicitis

Background

The pathogenesis of appendicitis is unclear. We evaluated whether exposure to air pollution was associated with an increased incidence of appendicitis.

Methods

We identified 5191 adults who had been admitted to hospital with appendicitis between Apr. 1, 1999, and Dec. 31, 2006. The air pollutants studied were ozone, nitrogen dioxide, sulfur dioxide, carbon monoxide, and suspended particulate matter of less than 10 μ and less than 2.5 μ in diameter. We estimated the odds of appendicitis relative to short-term increases in concentrations of selected pollutants, alone and in combination, after controlling for temperature and relative humidity as well as the effects of age, sex and season.

Results

An increase in the interquartile range of the 5-day average of ozone was associated with appendicitis (odds ratio [OR] 1.14, 95% confidence interval [CI] 1.03–1.25). In summer (July–August), the effects were most pronounced for ozone (OR 1.32, 95% CI 1.10–1.57), sulfur dioxide (OR 1.30, 95% CI 1.03–1.63), nitrogen dioxide (OR 1.76, 95% CI 1.20–2.58), carbon monoxide (OR 1.35, 95% CI 1.01–1.80) and particulate matter less than 10 μ in diameter (OR 1.20, 95% CI 1.05–1.38). We observed a significant effect of the air pollutants in the summer months among men but not among women (e.g., OR for increase in the 5-day average of nitrogen dioxide 2.05, 95% CI 1.21–3.47, among men and 1.48, 95% CI 0.85–2.59, among women). The double-pollutant model of exposure to ozone and nitrogen dioxide in the summer months was associated with attenuation of the effects of ozone (OR 1.22, 95% CI 1.01–1.48) and nitrogen dioxide (OR 1.48, 95% CI 0.97–2.24).

Interpretation

Our findings suggest that some cases of appendicitis may be triggered by short-term exposure to air pollution. If these findings are confirmed, measures to improve air quality may help to decrease rates of appendicitis.Appendicitis was introduced into the medical vernacular in 1886.¹ Since then, the prevailing theory of its pathogenesis implicated an obstruction of the appendiceal orifice by a fecalith or lymphoid hyperplasia.² However, this notion does not completely account for variations in incidence observed by age,^3,4 sex,^3,4 ethnic background,^3,4 family history,⁵ temporal–spatial clustering⁶ and seasonality,^3,4 nor does it completely explain the trends in incidence of appendicitis in developed and developing nations.^3,7,8The incidence of appendicitis increased dramatically in industrialized nations in the 19th century and in the early part of the 20th century.¹ Without explanation, it decreased in the middle and latter part of the 20th century.³ The decrease coincided with legislation to improve air quality. For example, after the United States Clean Air Act was passed in 1970,⁹ the incidence of appendicitis decreased by 14.6% from 1970 to 1984.³ Likewise, a 36% drop in incidence was reported in the United Kingdom between 1975 and 1994¹⁰ after legislation was passed in 1956 and 1968 to improve air quality and in the 1970s to control industrial sources of air pollution. Furthermore, appendicitis is less common in developing nations; however, as these countries become more industrialized, the incidence of appendicitis has been increasing.⁷Air pollution is known to be a risk factor for multiple conditions, to exacerbate disease states and to increase all-cause mortality.¹¹ It has a direct effect on pulmonary diseases such as asthma¹¹ and on nonpulmonary diseases including myocardial infarction, stroke and cancer.^11–13 Inflammation induced by exposure to air pollution contributes to some adverse health effects.^14–17 Similar to the effects of air pollution, a proinflammatory response has been associated with appendicitis.^18–20We conducted a case–crossover study involving a population-based cohort of patients admitted to hospital with appendicitis to determine whether short-term increases in concentrations of selected air pollutants were associated with hospital admission because of appendicitis.     

Effect of marriage on duration of chest pain associated with acute myocardial infarction before seeking care

Background:

Coronary artery disease is the most common cause of death in the Western world, and being married decreases the risk of death from cardiovascular causes. We aimed to determine whether marital status was a predictor of the duration of chest pain endured by patients with acute myocardial infarction before they sought care and whether the patient’s sex modified the effect.

Methods:

We conducted a retrospective, population-based cohort analysis of patients with acute myocardial infarction admitted to 96 acute care hospitals in Ontario, Canada, from April 2004 to March 2005. We excluded patients who did not experience chest pain. Using multivariable regression analyses, we assessed marital status in relation to delayed presentation to hospital (more than six hours from onset of pain), both overall and stratified by sex. In patients who reported the exact duration of chest pain, we assessed the effect of marital status on the delay in seeking care.

Results:

Among 4403 eligible patients with acute myocardial infarction, the mean age was 67.3 (standard deviation 13.6) years, and 1486 (33.7%) were women. Almost half (2037 or 46.3%) presented to a hospital within two hours, and 3240 (73.6%) presented within six hours. Overall, 75.3% (2317/3079) of married patients, 67.9% (188/277) of single patients, 68.5% (189/276) of divorced patients and 70.8% (546/771) of widowed patients presented within six hours of the onset of chest pain. Being married was associated with lower odds of delayed presentation (odds ratio [OR] 0.46, 95% confidence interval [CI] 0.30–0.71, p < 0.001) relative to being single. Among men, the OR was 0.35 (95% CI 0.21–0.59, p < 0.001), whereas among women the effect of marital status was not significant (OR 1.36, 95% CI 0.49–3.73, p = 0.55).

Interpretation:

Among men experiencing acute myocardial infarction with chest pain, being married was associated with significantly earlier presentation for care, a benefit that was not observed for married women. Earlier presentation for medical care appears to be one reason for the observed lower risk of cardiovascular death among married men, relative to their single counterparts.Marriage has long been known to offer health benefits^1,2 and is associated with a lower risk of death^3,4 relative to people who are not married. The effect is more pronounced among men than among women.^5,6 However, the specific mechanisms responsible for the lower rate of cardiovascular deaths in married persons⁷ are not known.Effective, time-sensitive therapy for acute myocardial infarction is available,^8,9 and delays in the emergency department and for in-hospital components of care have been substantially reduced over the past few decades.^10,11 In contrast, patients’ delay in seeking care for acute myocardial infarction has shown little improvement over time,^12,13 despite intensive campaigns to raise public awareness.^14,15 Patients’ delay remains by far the largest component of the overall delay between onset of symptoms and receipt of therapy.¹⁶ No study has examined the effect of marital status on patients’ delay, and only a few small studies have examined predictors of this component of delay by sex.^17,18We examined the effect of marital status, a social factor, on the time from onset of chest pain to arrival in an emergency department or hospital, in a population-based cohort of patients with acute myocardial infarction. We hypothesized that being married or in a common-law relationship would be associated with less delay, because we surmised that a spouse would encourage earlier pursuit of medical care, either directly or indirectly (i.e., even if the spouse was not physically present during the symptoms, his or her existence might spur the patient to seek care earlier). We hypothesized that wives would be more likely than husbands to assume the caregiver role and that the beneficial effect of marriage would therefore be stronger among men than among women.     

Effectiveness of interventions designed to reduce the use of imaging for low-back pain: a systematic review

Background:Rates of imaging for low-back pain are high and are associated with increased health care costs and radiation exposure as well as potentially poorer patient outcomes. We conducted a systematic review to investigate the effectiveness of interventions aimed at reducing the use of imaging for low-back pain.Methods:We searched MEDLINE, Embase, CINAHL and the Cochrane Central Register of Controlled Trials from the earliest records to June 23, 2014. We included randomized controlled trials, controlled clinical trials and interrupted time series studies that assessed interventions designed to reduce the use of imaging in any clinical setting, including primary, emergency and specialist care. Two independent reviewers extracted data and assessed risk of bias. We used raw data on imaging rates to calculate summary statistics. Study heterogeneity prevented meta-analysis.Results:A total of 8500 records were identified through the literature search. Of the 54 potentially eligible studies reviewed in full, 7 were included in our review. Clinical decision support involving a modified referral form in a hospital setting reduced imaging by 36.8% (95% confidence interval [CI] 33.2% to 40.5%). Targeted reminders to primary care physicians of appropriate indications for imaging reduced referrals for imaging by 22.5% (95% CI 8.4% to 36.8%). Interventions that used practitioner audits and feedback, practitioner education or guideline dissemination did not significantly reduce imaging rates. Lack of power within some of the included studies resulted in lack of statistical significance despite potentially clinically important effects.Interpretation:Clinical decision support in a hospital setting and targeted reminders to primary care doctors were effective interventions in reducing the use of imaging for low-back pain. These are potentially low-cost interventions that would substantially decrease medical expenditures associated with the management of low-back pain.Current evidence-based clinical practice guidelines recommend against the routine use of imaging in patients presenting with low-back pain.^1–3 Despite this, imaging rates remain high,^4,5 which indicates poor concordance with these guidelines.^6,7Unnecessary imaging for low-back pain has been associated with poorer patient outcomes, increased radiation exposure and higher health care costs.⁸ No short- or long-term clinical benefits have been shown with routine imaging of the low back, and the diagnostic value of incidental imaging findings remains uncertain.^9–12 A 2008 systematic review found that imaging accounted for 7% of direct costs associated with low-back pain, which in 1998 translated to more than US$6 billion in the United States and £114 million in the United Kingdom.¹³ Current costs are likely to be substantially higher, with an estimated 65% increase in spine-related expenditures between 1997 and 2005.¹⁴Various interventions have been tried for reducing imaging rates among people with low-back pain. These include strategies targeted at the practitioner such as guideline dissemination,^15–17 education workshops,^18,19 audit and feedback of imaging use,^7,20,21 ongoing reminders⁷ and clinical decision support.^22–24 It is unclear which, if any, of these strategies are effective.²⁵ We conducted a systematic review to investigate the effectiveness of interventions designed to reduce imaging rates for the management of low-back pain.     

Effect of nasal balloon autoinflation in children with otitis media with effusion in primary care: an open randomized controlled trial

Background:Otitis media with effusion is a common problem that lacks an evidence-based nonsurgical treatment option. We assessed the clinical effectiveness of treatment with a nasal balloon device in a primary care setting.Methods:We conducted an open, pragmatic randomized controlled trial set in 43 family practices in the United Kingdom. Children aged 4–11 years with a recent history of ear symptoms and otitis media with effusion in 1 or both ears, confirmed by tympanometry, were allocated to receive either autoinflation 3 times daily for 1–3 months plus usual care or usual care alone. Clearance of middle-ear fluid at 1 and 3 months was assessed by experts masked to allocation.Results:Of 320 children enrolled, those receiving autoinflation were more likely than controls to have normal tympanograms at 1 month (47.3% [62/131] v. 35.6% [47/132]; adjusted relative risk [RR] 1.36, 95% confidence interval [CI] 0.99 to 1.88) and at 3 months (49.6% [62/125] v. 38.3% [46/120]; adjusted RR 1.37, 95% CI 1.03 to 1.83; number needed to treat = 9). Autoinflation produced greater improvements in ear-related quality of life (adjusted between-group difference in change from baseline in OMQ-14 [an ear-related measure of quality of life] score −0.42, 95% CI −0.63 to −0.22). Compliance was 89% at 1 month and 80% at 3 months. Adverse events were mild, infrequent and comparable between groups.Interpretation:Autoinflation in children aged 4–11 years with otitis media with effusion is feasible in primary care and effective both in clearing effusions and improving symptoms and ear-related child and parent quality of life. Trial registration: ISRCTN, No. 55208702.Otitis media with effusion, also known as glue ear, is an accumulation of fluid in the middle ear, without symptoms or signs of an acute ear infection. It is often associated with viral infection.^1–3 The prevalence rises to 46% in children aged 4–5 years,⁴ when hearing difficulty, other ear-related symptoms and broader developmental concerns often bring the condition to medical attention.^3,5,6 Middle-ear fluid is associated with conductive hearing losses of about 15–45 dB HL.⁷ Resolution is clinically unpredictable,^8–10 with about a third of cases showing recurrence.¹¹ In the United Kingdom, about 200 000 children with the condition are seen annually in primary care.^12,13 Research suggests some children seen in primary care are as badly affected as those seen in hospital.^7,9,14,15 In the United States, there were 2.2 million diagnosed episodes in 2004, costing an estimated $4.0 billion.¹⁶ Rates of ventilation tube surgery show variability between countries,^17–19 with a declining trend in the UK.²⁰Initial clinical management consists of reasonable temporizing or delay before considering surgery.¹³ Unfortunately, all available medical treatments for otitis media with effusion such as antibiotics, antihistamines, decongestants and intranasal steroids are ineffective and have unwanted effects, and therefore cannot be recommended.^21–23 Not only are antibiotics ineffective, but resistance to them poses a major threat to public health.^24,25 Although surgery is effective for a carefully selected minority,^13,26,27 a simple low-cost, nonsurgical treatment option could benefit a much larger group of symptomatic children, with the purpose of addressing legitimate clinical concerns without incurring excessive delays.Autoinflation using a nasal balloon device is a low-cost intervention with the potential to be used more widely in primary care, but current evidence of its effectiveness is limited to several small hospital-based trials²⁸ that found a higher rate of tympanometric resolution of ear fluid at 1 month.^29–31 Evidence of feasibility and effectiveness of autoinflation to inform wider clinical use is lacking.^13,28 Thus we report here the findings of a large pragmatic trial of the clinical effectiveness of nasal balloon autoinflation in a spectrum of children with clinically confirmed otitis media with effusion identified from primary care.     

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.     

Influence of individual and combined healthy behaviours on successful aging

Background:

Increases in life expectancy make it important to remain healthy for as long as possible. Our objective was to examine the extent to which healthy behaviours in midlife, separately and in combination, predict successful aging.

Methods:

We used a prospective cohort design involving 5100 men and women aged 42–63 years. Participants were free of cancer, coronary artery disease and stroke when their health behaviours were assessed in 1991–1994 as part of the Whitehall II study. We defined healthy behaviours as never smoking, moderate alcohol consumption, physical activity (≥ 2.5 h/wk moderate physical activity or ≥ 1 h/wk vigorous physical activity), and eating fruits and vegetables daily. We defined successful aging, measured over a median 16.3-year follow-up, as good cognitive, physical, respiratory and cardiovascular functioning, in addition to the absence of disability, mental health problems and chronic disease (coronary artery disease, stroke, cancer and diabetes).

Results:

At the end of follow-up, 549 participants had died and 953 qualified as aging successfully. Compared with participants who engaged in no healthy behaviours, participants engaging in all 4 healthy behaviours had 3.3 times greater odds of successful aging (95% confidence interval [CI] 2.1–5.1). The association with successful aging was linear, with the odds ratio (OR) per increment of healthy behaviour being 1.3 (95% CI 1.2–1.4; population-attributable risk for 1–4 v. 0 healthy behaviours 47%). When missing data were considered in the analysis, the results were similar to those of our main analysis.

Interpretation:

Although individual healthy behaviours are moderately associated with successful aging, their combined impact is substantial. We did not investigate the mechanisms underlying these associations, but we saw clear evidence of the importance of healthy behaviours for successful aging.Increases in life expectancy make remaining free of disease and in good functional health for as long as possible an important objective for the present and future generations.¹ Most research in this domain has focused on risk factors for single health outcomes, such as mortality, chronic diseases or functioning. However, good health at older ages is a multidimensional concept, having been defined variously with reference to absence of disease and good functional status.^2–5 There is considerable research on disability outcomes at older ages,^2,6–8 but less attention has been paid to successful aging combining favourable functioning outcomes with good mental health and the absence of chronic diseases and disability.^9–13Smoking, alcohol consumption, poor diet and physical inactivity are among the top 10 leading risk factors for death and disability in intermediate- and high-income countries.¹⁴ There is increasing interest in the combined effect of these behaviours on health. Studies show that people who engage in multiple unhealthy behaviours have a higher risk of death,^15–23 chronic disease^24–30 and poor cognitive function than people who do not engage in as many unhealthy behaviours.³¹ However, whether healthy behaviours determine good functional status at older ages, combined with the absence of chronic diseases, remains unknown.Our objective was to examine the extent to which individual and combined healthy behaviours in midlife predict successful aging about 16 years later, at 60 years of age or older. We used a comprehensive definition of successful aging that included having good mental health, having good cognitive, physical and cardiorespiratory function, and being free of disability and chronic disease (coronary artery disease, stroke, diabetes and cancer).     

Suicide among children and adolescents in Canada: trends and sex differences, 1980�C2008

Background:

Suicide is the second leading cause of death for young Canadians (10–19 years of age) — a disturbing trend that has shown little improvement in recent years. Our objective was to examine suicide trends among Canadian children and adolescents.

Methods:

We conducted a retrospective analysis of standardized suicide rates using Statistics Canada mortality data for the period spanning from 1980 to 2008. We analyzed the data by sex and by suicide method over time for two age groups: 10–14 year olds (children) and 15–19 year olds (adolescents). We quantified annual trends by calculating the average annual percent change (AAPC).

Results:

We found an average annual decrease of 1.0% (95% confidence interval [CI] −1.5 to −0.4) in the suicide rate for children and adolescents, but stratification by age and sex showed significant variation. We saw an increase in suicide by suffocation among female children (AAPC = 8.1%, 95% CI 6.0 to 10.4) and adolescents (AAPC = 8.0%, 95% CI 6.2 to 9.8). In addition, we noted a decrease in suicides involving poisoning and firearms during the study period.

Interpretation:

Our results show that suicide rates in Canada are increasing among female children and adolescents and decreasing among male children and adolescents. Limiting access to lethal means has some potential to mitigate risk. However, suffocation, which has become the predominant method for committing suicide for these age groups, is not amenable to this type of primary prevention.Suicide was ranked as the second leading cause of death among Canadians aged 10–34 years in 2008.¹ It is recognized that suicidal behaviour and ideation is an important public health issue among children and adolescents; disturbingly, suicide is a leading cause of Canadian childhood mortality (i.e., among youths aged 10–19 years).^2,3Between 1980 and 2008, there were substantial improvements in mortality attributable to unintentional injury among 10–19 year olds, with rates decreasing from 37.7 per 100 000 to 10.7 per 100 000; suicide rates, however, showed less improvement, with only a small reduction during the same period (from 6.2 per 100 000 in 1980 to 5.2 per 100 000 in 2008).¹Previous studies that looked at suicides among Canadian adolescents and young adults (i.e., people aged 15–25 years) have reported rates as being generally stable over time, but with a marked increase in suicides by suffocation and a decrease in those involving firearms.² There is limited literature on self-inflicted injuries among children 10–14 years of age in Canada and the United States, but there appears to be a trend toward younger children starting to self-harm.^3,4 Furthermore, the trend of suicide by suffocation moving to younger ages may be partly due to cases of the “choking game” (self-strangulation without intent to cause permanent harm) that have been misclassified as suicides.^5–7Risk factors for suicidal behaviour and ideation in young people include a psychiatric diagnosis (e.g., depression), substance abuse, past suicidal behaviour, family factors and other life stressors (e.g., relationships, bullying) that have complex interactions.⁸ A suicide attempt involves specific intent, plans and availability of lethal means, such as firearms,⁹ elevated structures¹⁰ or substances.¹¹ The existence of “pro-suicide” sites on the Internet and in social media¹² may further increase risk by providing details of various ways to commit suicide, as well as evaluations ranking these methods by effectiveness, amount of pain involved and length of time to produce death.^13–15Our primary objective was to present the patterns of suicide among children and adolescents (aged 10–19 years) in Canada.     

Performance of the immunochemical fecal occult blood test in predicting lesions in the lower gastrointestinal tract

Background:

Previous studies have suggested that the immunochemical fecal occult blood test has superior specificity for detecting bleeding in the lower gastrointestinal tract even if bleeding occurs in the upper tract. We conducted a large population-based study involving asymptomatic adults in Taiwan, a population with prevalent upper gastrointestinal lesions, to confirm this claim.

Methods:

We conducted a prospective cohort study involving asymptomatic people aged 18 years or more in Taiwan recruited to undergo an immunochemical fecal occult blood test, colonoscopy and esophagogastroduodenoscopy between August 2007 and July 2009. We compared the prevalence of lesions in the lower and upper gastrointestinal tracts between patients with positive and negative fecal test results. We also identified risk factors associated with a false-positive fecal test result.

Results:

Of the 2796 participants, 397 (14.2%) had a positive fecal test result. The sensitivity of the test for predicting lesions in the lower gastrointestinal tract was 24.3%, the specificity 89.0%, the positive predictive value 41.3%, the negative predictive value 78.7%, the positive likelihood ratio 2.22, the negative likelihood ratio 0.85 and the accuracy 73.4%. The prevalence of lesions in the lower gastrointestinal tract was higher among those with a positive fecal test result than among those with a negative result (41.3% v. 21.3%, p < 0.001). The prevalence of lesions in the upper gastrointestinal tract did not differ significantly between the two groups (20.7% v. 17.5%, p = 0.12). Almost all of the participants found to have colon cancer (27/28, 96.4%) had a positive fecal test result; in contrast, none of the three found to have esophageal or gastric cancer had a positive fecal test result (p < 0.001). Among those with a negative finding on colonoscopy, the risk factors associated with a false-positive fecal test result were use of antiplatelet drugs (adjusted odds ratio [OR] 2.46, 95% confidence interval [CI] 1.21–4.98) and a low hemoglobin concentration (adjusted OR 2.65, 95% CI 1.62–4.33).

Interpretation:

The immunochemical fecal occult blood test was specific for predicting lesions in the lower gastrointestinal tract. However, the test did not adequately predict lesions in the upper gastrointestinal tract.The fecal occult blood test is a convenient tool to screen for asymptomatic gastrointestinal bleeding.¹ When the test result is positive, colonoscopy is the strategy of choice to investigate the source of bleeding.^2,3 However, 13%–42% of patients can have a positive test result but a negative colonoscopy,⁴ and it has not yet been determined whether asymptomatic patients should then undergo evaluation of the upper gastrointestinal tract.Previous studies showed that the frequency of lesions in the upper gastrointestinal tract was comparable or even higher than that of colonic lesions^5–9 and that the use of esophagogastroduodenoscopy may change clinical management.^10,11 Some studies showed that evaluation of the upper gastrointestinal tract helped to identify important lesions in symptomatic patients and those with iron deficiency anemia;^12,13 however, others concluded that esophagogastroduodenoscopy was unjustified because important findings in the upper gastrointestinal tract were rare^14–17 and sometimes irrelevant to the results of fecal occult blood testing.^18–21 This controversy is related to the heterogeneity of study populations and to the limitations of the formerly used guaiac-based fecal occult blood test,^5–20 which was not able to distinguish bleeding in the lower gastrointestinal tract from that originating in the upper tract.The guaiac-based fecal occult blood test is increasingly being replaced by the immunochemical-based test. The latter is recommended for detecting bleeding in the lower gastrointestinal tract because it reacts with human globin, a protein that is digested by enzymes in the upper gastrointestinal tract.²² With this advantage, the occurrence of a positive fecal test result and a negative finding on colonoscopy is expected to decrease.We conducted a population-based study in Taiwan to verify the performance of the immunochemical fecal occult blood test in predicting lesions in the lower gastrointestinal tract and to confirm that results are not confounded by the presence of lesions in the upper tract. In Taiwan, the incidence of colorectal cancer is rapidly increasing, and Helicobacter pylori-related lesions in the upper gastrointestinal tract remain highly prevalent.²³ Same-day bidirectional endoscopies are therefore commonly used for cancer screening.²⁴ This screening strategy provides an opportunity to evaluate the performance of the immunochemical fecal occult blood test.     

Predictors of long-term prognosis of depression

Background:

Many people with depression experience repeated episodes. Previous research into the predictors of chronic depression has focused primarily on the clinical features of the disease; however, little is known about the broader spectrum of sociodemographic and health factors inherent in its development. Our aim was to identify factors associated with a long-term negative prognosis of depression.

Methods:

We included 585 people aged 16 years and older who participated in the 2000/01 cycle of the National Population Health Survey and who reported experiencing a major depressive episode in 2000/01. The primary outcome was the course of depression until 2006/07. We grouped individuals into trajectories of depression using growth trajectory models. We included demographic, mental and physical health factors as predictors in the multivariable regression model to compare people with different trajectories.

Results:

Participants fell into two main depression trajectories: those whose depression resolved and did not recur (44.7%) and those who experienced repeated episodes (55.3%). In the multivariable model, daily smoking (OR 2.68, 95% CI 1.54–4.67), low mastery (i.e., feeling that life circumstances are beyond one’s control) (OR 1.10, 95% CI 1.03–1.18) and history of depression (OR 3.5, 95% CI 1.95–6.27) were significant predictors (p < 0.05) of repeated episodes of depression.

Interpretation:

People with major depression who were current smokers or had low levels of mastery were at an increased risk of repeated episodes of depression. Future studies are needed to confirm the predictive value of these variables and to evaluate their accuracy for diagnosis and as a guide to treatment.Depression is a common and often recurrent disorder that compromises daily functioning and is associated with a decrease in quality of life.^1–3 Guidelines for the treatment of depression, such as those published by the Canadian Network for Mood and Anxiety Treatments (CANMAT)⁵ and the National Institute for Health and Clinical Excellence (NICE) in the United Kingdom,⁴ often recommend antidepressant treatment in patients with severe symptoms and outline specific risk factors supporting long-term treatment maintenance.^4,5 However, for patients who do not meet the criteria for treatment of depression, the damaging sequelae of depression are frequently compounded without treatment.⁵ In such cases, early treatment for depression may result in an improved long-term prognosis.^6–8A small but growing number of studies have begun to characterize the long-term course of depression in terms of severity,⁹ life-time prevalence¹⁰ and patterns of recurrence.¹¹ However, a recent systematic review of the risk factors of chronic depression highlighted a need for longitudinal studies to better identify prognostic factors.¹² The capacity to distinguish long-term patterns of recurrence of depression in relation to the wide range of established clinical and nonclinical factors for depression could be highly beneficial. Our objective was to use a population-based cohort to identify and understand the baseline factors associated with a long-term negative prognosis of depression.     

Cardiovascular disease after Escherichia coli O157:H7 gastroenteritis

Background:

Escherichia coli O157:H7 is one cause of acute bacterial gastroenteritis, which can be devastating in outbreak situations. We studied the risk of cardiovascular disease following such an outbreak in Walkerton, Ontario, in May 2000.

Methods:

In this community-based cohort study, we linked data from the Walkerton Health Study (2002–2008) to Ontario’s large healthcare databases. We included 4 groups of adults: 3 groups of Walkerton participants (153 with severe gastroenteritis, 414 with mild gastroenteritis, 331 with no gastroenteritis) and a group of 11 263 residents from the surrounding communities that were unaffected by the outbreak. The primary outcome was a composite of death or first major cardiovascular event (admission to hospital for acute myocardial infarction, stroke or congestive heart failure, or evidence of associated procedures). The secondary outcome was first major cardiovascular event censored for death. Adults were followed for an average of 7.4 years.

Results:

During the study period, 1174 adults (9.7%) died or experienced a major cardiovascular event. Compared with residents of the surrounding communities, the risk of death or cardiovascular event was not elevated among Walkerton participants with severe or mild gastroenteritis (hazard ratio [HR] for severe gastroenteritis 0.74, 95% confidence interval [CI] 0.38–1.43, mild gastroenteritis HR 0.64, 95% CI 0.42–0.98). Compared with Walkerton participants who had no gastroenteritis, risk of death or cardiovascular event was not elevated among participants with severe or mild gastroenteritis.

Interpretation:

There was no increase in the risk of cardiovascular disease in the decade following acute infection during a major E. coli O157:H7 outbreak.Escherichia coli O157:H7 is one cause of acute bacterial gastroenteritis, causing 63 000 infections each year and 12 major outbreaks since 2006 in the United States alone.^1,2 This strain was most recently implicated in the outbreak involving beef from XL Foods (September 2012), with 17 confirmed cases across Canada.³ A similar enterohemorrhagic strain E. coli O104:H4 was responsible for an outbreak in Germany in May 2011, causing 3792 cases of gastroenteritis and 43 deaths.^4,5Most patients fully recover from acute gastroenteritis caused by E. coli. However, such an illness may predispose patients to long-term disease. Shiga toxin is produced by E. coli O157:H7; this toxin damages the microvasculature of the kidneys leading to hypertension^6–13 and directly damages the systemic vasculature.^14–16 Infected people may progress from a state of acute inflammation of the vasculature to subclinical chronic inflammation, which could promote atherosclerosis.^17–20In Walkerton, Ontario, in May 2000, heavy rains transported bovine fecal matter into the town’s well, contaminating the inadequately chlorinated municipal water supply with E. coli O157:H7.²¹ Over 2300 people developed acute gastroenteritis, and 7 people died.²² The unique circumstances of this outbreak provided a rare opportunity to study the natural history following exposure to this pathogen in a single cohort.²³ Other outbreaks have been geographically dispersed, making it difficult to track cases.^24,25In Walkerton, affected individuals were followed annually in a clinic to assess their long-term outcomes (Walkerton Health Study, 2002–2008). We previously reported that adults who experienced acute gastroenteritis during the outbreak had a higher than expected incidence of hypertension, chronic kidney disease and self-reported cardiovascular disease in follow-up.²³ However, 46% of participants were lost to follow-up by the end of the study, and there were limitations associated with the assessment of cardiovascular disease by participant recall. Thus, we conducted an expanded and extended follow-up study, linking the Walkerton study data to Ontario’s health care databases. Our objective was to more accurately determine the 10-year risk of major cardiovascular events after exposure to E. coli O157:H7.