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.     

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.     

Effectiveness of training family physicians to deliver a brief intervention to address excessive substance use among young patients: a cluster randomized controlled trial

Background:

Brief interventions delivered by family physicians to address excessive alcohol use among adult patients are effective. We conducted a study to determine whether such an intervention would be similarly effective in reducing binge drinking and excessive cannabis use among young people.

Methods:

We conducted a cluster randomized controlled trial involving 33 family physicians in Switzerland. Physicians in the intervention group received training in delivering a brief intervention to young people during the consultation in addition to usual care. Physicians in the control group delivered usual care only. Consecutive patients aged 15–24 years were recruited from each practice and, before the consultation, completed a confidential questionnaire about their general health and substance use. Patients were followed up at 3, 6 and 12 months after the consultation. The primary outcome measure was self-reported excessive substance use (≥ 1 episode of binge drinking, or ≥ 1 joint of cannabis per week, or both) in the past 30 days.

Results:

Of the 33 participating physicians, 17 were randomly allocated to the intervention group and 16 to the control group. Of the 594 participating patients, 279 (47.0%) identified themselves as binge drinkers or excessive cannabis users, or both, at baseline. Excessive substance use did not differ significantly between patients whose physicians were in the intervention group and those whose physicians were in the control group at any of the follow-up points (odds ratio [OR] and 95% confidence interval [CI] at 3 months: 0.9 [0.6–1.4]; at 6 mo: 1.0 [0.6–1.6]; and at 12 mo: 1.1 [0.7–1.8]). The differences between groups were also nonsignificant after we re stricted the analysis to patients who reported excessive substance use at baseline (OR 1.6, 95% CI 0.9–2.8, at 3 mo; OR 1.7, 95% CI 0.9–3.2, at 6 mo; and OR 1.9, 95% CI 0.9–4.0, at 12 mo).

Interpretation:

Training family physicians to use a brief intervention to address excessive substance use among young people was not effective in reducing binge drinking and excessive cannabis use in this patient population. Trial registration: Australian New Zealand Clinical Trials Registry, no. ACTRN12608000432314.Most health-compromising behaviours begin in adolescence.¹ Interventions to address these behaviours early are likely to bring long-lasting benefits.² Harmful use of alcohol is a leading factor associated with premature death and disability worldwide, with a disproportionally high impact on young people (aged 10–24 yr).^3,4 Similarly, early cannabis use can have adverse consequences that extend into adulthood.^5–8In adolescence and early adulthood, binge drinking on at least a monthly basis is associated with an increased risk of adverse outcomes later in life.^9–12 Although any cannabis use is potentially harmful, weekly use represents a threshold in adolescence related to an increased risk of cannabis (and tobacco) dependence in adulthood.¹³ Binge drinking affects 30%–50% and excessive cannabis use about 10% of the adolescent and young adult population in Europe and the United States.^10,14,15Reducing substance-related harm involves multisectoral approaches, including promotion of healthy child and adolescent development, regulatory policies and early treatment interventions.¹⁶ Family physicians can add to the public health messages by personalizing their content within brief interventions.^17,18 There is evidence that brief interventions can encourage young people to reduce substance use, yet most studies have been conducted in community settings (mainly educational), emergency services or specialized addiction clinics.^1,16 Studies aimed at adult populations have shown favourable effects of brief alcohol interventions, and to some extent brief cannabis interventions, in primary care.^19–22 These interventions have been recommended for adolescent populations.^4,5,16 Yet young people have different modes of substance use and communication styles that may limit the extent to which evidence from adult studies can apply to them.Recently, a systematic review of brief interventions to reduce alcohol use in adolescents identified only 1 randomized controlled trial in primary care.²³ The tested intervention, not provided by family physicians but involving audio self-assessment, was ineffective in reducing alcohol use in exposed adolescents.²⁴ Sanci and colleagues showed that training family physicians to address health-risk behaviours among adolescents was effective in improving provider performance, but the extent to which this translates into improved outcomes remains unknown.^25,26 Two nonrandomized studies suggested screening for substance use and brief advice by family physicians could favour reduced alcohol and cannabis use among adolescents,^27,28 but evidence from randomized trials is lacking.²⁹We conducted the PRISM-Ado (Primary care Intervention Addressing Substance Misuse in Adolescents) trial, a cluster randomized controlled trial of the effectiveness of training family physicians to deliver a brief intervention to address binge drinking and excessive cannabis use among young people.     

Effect of dietary pulse intake on established therapeutic lipid targets for cardiovascular risk reduction: a systematic review and meta-analysis of randomized controlled trials

Background:

Evidence from controlled trials encourages the intake of dietary pulses (beans, chickpeas, lentils and peas) as a method of improving dyslipidemia, but heart health guidelines have stopped short of ascribing specific benefits to this type of intervention or have graded the beneficial evidence as low. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the effect of dietary pulse intake on established therapeutic lipid targets for cardiovascular risk reduction.

Methods:

We searched electronic databases and bibliographies of selected trials for relevant articles published through Feb. 5, 2014. We included RCTs of at least 3 weeks’ duration that compared a diet emphasizing dietary pulse intake with an isocaloric diet that did not include dietary pulses. The lipid targets investigated were low-density lipoprotein (LDL) cholesterol, apolipoprotein B and non–high-density lipoprotein (non-HDL) cholesterol. We pooled data using a random-effects model.

Results:

We identified 26 RCTs (n = 1037) that satisfied the inclusion criteria. Diets emphasizing dietary pulse intake at a median dose of 130 g/d (about 1 serving daily) significantly lowered LDL cholesterol levels compared with the control diets (mean difference −0.17 mmol/L, 95% confidence interval −0.25 to −0.09 mmol/L). Treatment effects on apolipoprotein B and non-HDL cholesterol were not observed.

Interpretation:

Our findings suggest that dietary pulse intake significantly reduces LDL cholesterol levels. Trials of longer duration and higher quality are needed to verify these results. Trial registration: ClinicalTrials.gov, no. {"type":"clinical-trial","attrs":{"text":"NCT01594567","term_id":"NCT01594567"}}NCT01594567.Abnormal blood concentrations of lipids are one of the most important modifiable risk factors for cardiovascular disease. Although statins are effective in reducing low-density lipoprotein (LDL) cholesterol levels, major health organizations have maintained that the initial and essential approach to the prevention and management of cardiovascular disease is to modify dietary and lifestyle patterns.^1–4Dietary non–oil-seed pulses (beans, chickpeas, lentils and peas) are foods that have received particular attention for their ability to reduce the risk of cardiovascular disease. Consumption of dietary pulses was associated with a reduction in cardiovascular disease in a large observational study⁵ and with improvements in LDL cholesterol levels in small trials.^6–8 Although most guidelines on the prevention of major chronic diseases encourage the consumption of dietary pulses as part of a healthy strategy,^2,3,9–13 none has included recommendations based on the direct benefits of lowering lipid concentrations or reducing the risk of cardiovascular disease. In all cases, the evidence on which recommendations have been based was assigned a low grade,^2,3,9–13 and dyslipidemia guidelines do not address dietary pulse intake directly.^1,4To improve the evidence on which dietary guidelines are based, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) of the effect of dietary pulse intake on established therapeutic lipid targets for cardiovascular risk reduction. The lipid targets were LDL cholesterol, apolipoprotein B and non–high-density lipoprotein (non-HDL) cholesterol.     

Effect of melatonin on incidence of delirium among patients with hip fracture: a multicentre,double-blind randomized controlled trial

Background:

Disturbance of the sleep–wake cycle is a characteristic of delirium. In addition, changes in melatonin rhythm influence the circadian rhythm and are associated with delirium. We compared the effect of melatonin and placebo on the incidence and duration of delirium.

Methods:

We performed this multicentre, double-blind, randomized controlled trial between November 2008 and May 2012 in 1 academic and 2 nonacademic hospitals. Patients aged 65 years or older who were scheduled for acute hip surgery were eligible for inclusion. Patients received melatonin 3 mg or placebo in the evening for 5 consecutive days, starting within 24 hours after admission. The primary outcome was incidence of delirium within 8 days of admission. We also monitored the duration of delirium.

Results:

A total of 452 patients were randomly assigned to the 2 study groups. We subsequently excluded 74 patients for whom the primary end point could not be measured or who had delirium before the second day of the study. After these postrandomization exclusions, data for 378 patients were included in the main analysis. The overall mean age was 84 years, 238 (63.0%) of the patients lived at home before admission, and 210 (55.6%) had cognitive impairment. We observed no effect of melatonin on the incidence of delirium: 55/186 (29.6%) in the melatonin group v. 49/192 (25.5%) in the placebo group; difference 4.1 (95% confidence interval −0.05 to 13.1) percentage points. There were no between-group differences in mortality or in cognitive or functional outcomes at 3-month follow-up.

Interpretation:

In this older population with hip fracture, treatment with melatonin did not reduce the incidence of delirium. Trial registration: Netherlands Trial Registry, NTR1576: MAPLE (Melatonin Against PLacebo in Elderly patients) study; www.trialregister.nl/trialreg/admin/rctview.asp?TC=1576Delirium in older inpatients is associated with a high risk of dementia and other complications that translate into increased mortality and health care costs.^1,2 The antipsychotic haloperidol has historically been the agent of choice for treating delirium, and it has increasingly been administered as a prophylactic for delirium or to reduce symptoms such as hallucinations and aggressive behaviour.^3,4 However, all antipsychotic treatments may induce serious cerebrovascular adverse effects and greater mortality, particularly among patients with dementia.^5,6 These effects led the US Food and Drug Administration to issue a serious warning against their use.⁷ In addition, benzodiazepines are still frequently used to treat delirium, despite their being known to elicit or aggravate delirium.^8,9Disturbances of the circadian sleep–wake cycle represent one of the core features of delirium,¹⁰ leading to the hypothesis that the neurotransmitter melatonin and changes in its metabolism may be involved in the pathogenesis of delirium.^11,12 Objective measurements have shown that melatonin metabolism is disturbed after abdominal and other types of surgery, insomnia, sleep deprivation and stays in the intensive care unit (ICU), all of which are also known to be factors that contribute to delirium.^13–16 These characteristics suggest an association between melatonin abnormalities and delirium.^17–22 Although proof of a causal relation is still lacking, inpatients might nevertheless benefit from melatonin supplementation therapy through postoperative maintenance or restoration of their sleep–wake cycle.^23–25 Although melatonin depletion is thought to be one of the mechanisms of delirium, few studies have investigated the effects of altering perioperative plasma concentrations of melatonin, in particular, the possible effects on postoperative delirium.The primary objective of this study was to assess the effects of melatonin on the incidence of delirium among elderly patients admitted to hospital as an emergency following hip fracture. Secondary outcomes were duration and severity of delirium, length of hospital stay, total doses of haloperidol and benzodiazepines administered to patients with delirium, mortality during the hospital stay, and functional status, cognitive function and mortality at 3-month follow-up.     

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.     

Effectiveness of quality improvement strategies for coordination of care to reduce use of health care services: a systematic review and meta-analysis

Background:

Frequent users of health care services are a relatively small group of patients who account for a disproportionately large amount of health care utilization. We conducted a meta-analysis of the effectiveness of interventions to improve the coordination of care to reduce health care utilization in this patient group.

Methods:

We searched MEDLINE, Embase and the Cochrane Library from inception until May 2014 for randomized clinical trials (RCTs) assessing quality improvement strategies for the coordination of care of frequent users of the health care system. Articles were screened, and data abstracted and appraised for quality by 2 reviewers, independently. Random effects meta-analyses were conducted.

Results:

We identified 36 RCTs and 14 companion reports (total 7494 patients). Significantly fewer patients in the intervention group than in the control group were admitted to hospital (relative risk [RR] 0.81, 95% confidence interval [CI] 0.72–0.91). In subgroup analyses, a similar effect was observed among patients with chronic medical conditions other than mental illness, but not among patients with mental illness. In addition, significantly fewer patients 65 years and older in the intervention group than in the control group visited emergency departments (RR 0.69, 95% CI 0.54–0.89).

Interpretation:

We found that quality improvement strategies for coordination of care reduced hospital admissions among patients with chronic conditions other than mental illness and reduced emergency department visits among older patients. Our results may help clinicians and policy-makers reduce utilization through the use of strategies that target the system (team changes, case management) and the patient (promotion of self-management).Frequent users of health care services represent a relatively small group of patients who account for a disproportionately large amount of health care utilization, including emergency department visits,^1,2 hospital admissions and clinic visits. These patients are often of low socioeconomic status,^3,4 have multiple medical, psychiatric and social disorders^5,6 and have a high mortality.⁷ Frequent use of the health care system contributes to longer wait times and affects the quality of care.^4,8Disproportionate use of health care services by a segment of the population has been identified as a challenge in many countries, including Canada.^9–12 To encourage less resource-intensive care for frequent users, many efforts have been implemented. Some of these interventions, for example, have been designed specifically to transition health care utilization away from the hospital to other settings, such as community-based clinics.¹³Much of the literature has focused on frequent users of emergency departments, with less focus on their use of the health care system in general. One systematic review identified a number of studies that assessed the effect of various interventions, including care coordination.¹⁴ The authors concluded that case management and multidisciplinary teams were likely effective interventions to reduce emergency department visits.Emergency department visits typically represent only a fraction of the cost burden on the health care system. There is a need to understand the impact of interventions aimed at reducing overall health care utilization, including hospital admissions. We conducted a systematic review and meta-analysis of the effectiveness of quality improvement strategies for care coordination for patients who are frequent users of the health care system.     

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.     

Validity of the diagnostic criteria for chronic cerebrospinal venous insufficiency and association with multiple sclerosis

Background:

The chronic cerebrospinal venous insufficiency theory proposes that altered cerebral venous hemodynamics play a role in the pathophysiology of multiple sclerosis. We aimed to explore the validity of this hypothesis by assessing the diagnostic criteria for chronic cerebrospinal venous insufficiency in persons with and without multiple sclerosis.

Methods:

We compared the proportion of venous outflow abnormalities between patients with multiple sclerosis and healthy controls using extracranial Doppler ultrasonography and gadolinium-enhanced magnetic resonance venography. Interpreting radiologists were blinded to the clinical status of participants.

Results:

We enrolled 120 patients with multiple sclerosis and 60 healthy controls. High proportions of both patients (67/115 [58%]) and controls (38/60 [63%]) met 1 or more of the proposed ultrasound criteria for diagnosis of chronic cerebrospinal venous insufficiency (p = 0.6). A minority of patients (23/115 [20%]) and controls (6/60 [10%]) fulfilled 2 or more of the proposed criteria (p = 0.1). There were no differences between patients and controls in the prevalence of each individual ultrasound criterion. Similarly, there were no differences in intracranial or extracranial venous patency between groups, as measured by magnetic resonance venography.

Interpretation:

We detected no differences in the proportion of venous outflow abnormalities between patients with multiple sclerosis and healthy controls. Moreover, our study revealed significant methodologic concerns regarding the proposed diagnostic criteria for chronic cerebrospinal venous insufficiency that challenge their validity.Multiple sclerosis is an inflammatory disease of the central nervous system, believed to arise from a dysfunctional immune-mediated response in a genetically susceptible host.¹ In 2009, “chronic cerebrospinal venous insufficiency” was proposed to play an etiologic role in multiple sclerosis.^2–4 Despite an abundance of published literature on this topic,^2–28 a causal link has not been established. Recent meta-analyses have suggested a strong association between an ultrasound-based diagnosis of chronic cerebrospinal venous insufficiency and multiple sclerosis,^26,28 yet there has been significant heterogeneity across studies.^26,27 A factor contributing to this heterogeneity appears to be the involvement of investigators who support endovascular procedures as a treatment for multiple sclerosis.²⁷ Furthermore, these meta-analyses have been predicated on the assumption that valid diagnostic criteria for chronic cerebrospinal venous insufficiency exist.We aimed to explore the validity of the chronic cerebrospinal venous insufficiency theory by using extracranial ultrasonography and gadolinium-enhanced magnetic resonance venography to compare the proportion of venous outflow abnormalities between patients with multiple sclerosis and healthy individuals. Our primary hypothesis was that if chronic cerebrospinal venous insufficiency is associated with multiple sclerosis, we would detect significant evidence of venous outflow obstruction in patients relative to controls.     

Reduction of radial-head subluxation in children by triage nurses in the emergency department: a cluster-randomized controlled trial

Background:

Radial-head subluxation is an easily identified and treated injury. We investigated whether triage nurses in the emergency department can safely reduce radial-head subluxation at rates that are not substantially lower than those of emergency department physicians.

Methods:

We performed an open, noninferiority, cluster-randomized control trial. Children aged 6 years and younger who presented to the emergency department with a presentation consistent with radial-head subluxation and who had sustained a known injury in the previous 12 hours were assigned to either nurse-initiated or physician-initiated treatment, depending on the day. The primary outcome was the proportion of children who had a successful reduction (return to normal arm usage). We used a noninferiority margin of 10%.

Results:

In total, 268 children were eligible for inclusion and 245 were included in the final analysis. Of the children assigned to receive physician-initiated care, 96.7% (117/121) had a successful reduction performed by a physician. Of the children assigned to receive nurse-treatment care, 84.7% (105/124) had a successful reduction performed by a nurse. The difference in the proportion of successful radial head subluxations between the groups was 12.0% (95% confidence interval [CI] 4.8% to 19.7%). Noninferiority of nurse-initiated radial head subluxation was not shown.

Interpretation:

In this trial, the rate of successful radial-head subluxation performed by nurses was inferior to the physician success rate. Although the success rate in the nurse-initiated care group did not meet the non-inferiority margin, nurses were able to reduce radial head subluxation for almost 85% of children who presented with probable radial-head subluxation. Trial registration: Clinical Trials.gov, no. {"type":"clinical-trial","attrs":{"text":"NCT00993954","term_id":"NCT00993954"}}NCT00993954.Radial-head subluxation is a common arm injury among young children and often results in a visit to the emergency department.¹ This type of injury occurs when forceful longitudinal traction is applied to an extended and pronated forearm.² Radial-head subluxation is easily recognized by its clinical presentation and can be treated by a simple reduction technique involving hyperpronation or supination and flexion of the injured arm.^3–7Despite the ease of diagnosis and treatment, children with radial-head subluxation often wait hours in the emergency department for a reduction that takes minutes to perform.⁸ These visits have direct health care costs and involve time and stress for the child and their family. Early treatment and shorter wait times correlate with patient satisfaction.^9,10 Patient satisfaction is comparable when minor injuries are cared for by a nurse instead of by a physician.^11–13 Nurse-initiated treatments are increasingly a focus of health care.^14–17Treatment of radial-head subluxation is an appropriate area to consider nurse-initiated care. Our objective was to determine whether triage nurses, trained in the recognition and treatment of radial-head subluxation, could successfully reduce radial-head subluxation at a rate similar to that of physicians.     

Smoked cannabis for chronic neuropathic pain: a randomized controlled trial

Background

Chronic neuropathic pain affects 1%–2% of the adult population and is often refractory to standard pharmacologic treatment. Patients with chronic pain have reported using smoked cannabis to relieve pain, improve sleep and improve mood.

Methods

Adults with post-traumatic or postsurgical neuropathic pain were randomly assigned to receive cannabis at four potencies (0%, 2.5%, 6% and 9.4% tetrahydrocannabinol) over four 14-day periods in a crossover trial. Participants inhaled a single 25-mg dose through a pipe three times daily for the first five days in each cycle, followed by a nine-day washout period. Daily average pain intensity was measured using an 11-point numeric rating scale. We recorded effects on mood, sleep and quality of life, as well as adverse events.

Results

We recruited 23 participants (mean age 45.4 [standard deviation 12.3] years, 12 women [52%]), of whom 21 completed the trial. The average daily pain intensity, measured on the 11-point numeric rating scale, was lower on the prespecified primary contrast of 9.4% v. 0% tetrahydrocannabinol (5.4 v. 6.1, respectively; difference = 0.7, 95% confidence interval [CI] 0.02–1.4). Preparations with intermediate potency yielded intermediate but nonsignificant degrees of relief. Participants receiving 9.4% tetrahydrocannabinol reported improved ability to fall asleep (easier, p = 0.001; faster, p < 0.001; more drowsy, p = 0.003) and improved quality of sleep (less wakefulness, p = 0.01) relative to 0% tetrahydrocannabinol. We found no differences in mood or quality of life. The most common drug-related adverse events during the period when participants received 9.4% tetrahydrocannabinol were headache, dry eyes, burning sensation in areas of neuropathic pain, dizziness, numbness and cough.

Conclusion

A single inhalation of 25 mg of 9.4% tetrahydrocannabinol herbal cannabis three times daily for five days reduced the intensity of pain, improved sleep and was well tolerated. Further long-term safety and efficacy studies are indicated. (International Standard Randomised Controlled Trial Register no. ISRCTN68314063)Chronic neuropathic pain has a prevalence of 1%–2%,¹ and treatment options are limited.² Pharmacotherapy includes anticonvulsants, antidepressants, opioids and local anesthetics,^3,4 but responses vary and side effects limit compliance.Cannabis sativa has been used to treat pain since the third millennium BC.⁵ An endogenous pain-processing system has been identified, mediated by endogenous cannabinoid ligands acting on specific cannabinoid receptors.⁶ These findings, coupled with anecdotal evidence of the analgesic effects of smoked cannabis,⁷ support a reconsideration of cannabinoid agents as analgesics.Oral cannabinoids such as tetrahydrocannabinol, cannabidiol and nabilone have, alone and in combination, shown efficacy in central^8,9 and peripheral¹⁰ neuropathic pain, rheumatoid arthritis¹¹ and fibromyalgia.¹²The analgesic effects of smoked cannabis remain controversial, although it is used by 10%–15% of patients with chronic noncancer pain¹³ and multiple sclerosis.¹⁴ Clinical trials are needed to evaluate these effects, given that the risks and benefits of inhaled cannabinoids may differ from oral agents. To date, three small clinical trials of the analgesic efficacy of smoked cannabis have been reported.^15–17 All studies were conducted in residential laboratories, and participants smoked multiple doses of the drug at each time point. No study adequately reported data related to adverse events.We conducted a clinical trial using a standardized single-dose delivery system to explore further the safety and efficacy of smoked cannabis in outpatients with chronic neuropathic pain.     

Rates and determinants of seasonal influenza vaccination in pregnancy and association with neonatal outcomes

Background:

There is growing evidence that seasonal influenza vaccination in pregnancy has benefits for mother and baby. We determined influenza vaccination rates among pregnant women during the 2 nonpandemic influenza seasons following the 2009 H1N1 pandemic, explored maternal factors as predictors of influenza vaccination status and evaluated the association between maternal influenza vaccination and neonatal outcomes.

Methods:

We used a population-based perinatal database in the province of Nova Scotia, Canada, to examine maternal vaccination rates, determinants of vaccination status and neonatal outcomes. Our cohort included women who gave birth between Nov. 1, 2010, and Mar. 31, 2012. We compared neonatal outcomes between vaccinated and unvaccinated women using logistic regression analysis.

Results:

Overall, 1958 (16.0%) of 12 223 women in our cohort received the influenza vaccine during their pregnancy. Marital status, parity, location of residence (rural v. urban), smoking during pregnancy and maternal influenza risk status were determinants of maternal vaccine receipt. The odds of preterm birth was lower among infants of vaccinated women than among those of nonvaccinated women (adjusted odds ratio [OR] 0.75, 95% confidence interval [CI] 0.60–0.94). The rate of low-birth-weight infants was also lower among vaccinated women (adjusted OR 0.73, 95% CI 0.56–0.95).

Interpretation:

Despite current guidelines advising all pregnant women to receive the seasonal influenza vaccine, influenza vaccination rates among pregnant women in our cohort were low in the aftermath of the 2009 H1N1 pandemic. This study and others have shown an association between maternal influenza vaccination and improved neonatal outcomes, which supports stronger initiatives to promote vaccination during pregnancy.Influenza viruses are the leading cause of serious wintertime respiratory morbidity worldwide. Several studies investigating the effects of influenza-related illness during pregnancy have shown a strong impact on the health of pregnant women in terms of increased rates of hospital admission because of respiratory illness.^1–3 Schanzer and colleagues² found that pregnant women in Canada were at increased risk of influenza-related hospital admission when compared with nonpregnant women of similar age and health status. In addition, influenza-related illness during pregnancy may have a negative impact on neonatal outcomes. A study in Nova Scotia, Canada, showed that infants whose mothers were admitted to hospital because of respiratory illness during influenza season while pregnant were more likely to be small for gestational age and to have lower mean birth weight.⁴By 2007, the cumulative evidence from these and other studies was compelling enough for advisory boards in Canada to recommend routine influenza vaccination for all pregnant women, including those without medical comorbidities.⁵ Despite these recommendations, seasonal vaccination rates among pregnant women have remained low. In a cohort of pregnant women who delivered at the IWK Health Centre, Halifax, from 2006 to 2009, only 20% had received the vaccine during their pregnancy.⁶ Increased vaccination rates among pregnant women were reported for the 2009 H1N1 pandemic year,⁷ but it is unknown whether this has translated into higher rates of seasonal influenza vaccination since then. Studies have shown that concern about vaccine safety is the most commonly cited reason for refusing the vaccine,^8,9 despite much evidence showing it to be safe in pregnancy.¹⁰ A recommendation from a maternity care provider has been shown to be a key factor in increasing vaccination rates.^11,12In light of the growing evidence that influenza vaccination during pregnancy has benefits for both the mother and the infant,^13–18 we evaluated rates of seasonal influenza vaccination among pregnant women in the 2 nonpandemic influenza seasons (2010/11 and 2011/12) following the 2009 H1N1 pandemic. We also assessed whether neonatal outcomes differed between women who received the vaccine during pregnancy and those who did not.     

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.     

Body size and physical activity in relation to incidence of chronic obstructive pulmonary disease

Background:

Limited evidence suggests that adiposity and lack of physical activity may increase the risk of chronic obstructive pulmonary disease (COPD). We investigated the relation of body size and physical activity with incidence of COPD.

Methods:

We obtained data on anthropometric measurements and physical activity from 113 279 participants in the National Institutes of Health–AARP Diet and Health Study who reported no diagnosis of COPD at baseline (1995–1996). We estimated associations between these measurements and subsequent diagnosis of COPD between 1996 and 2006, with extensive adjustment for smoking and other potentially confounding variables.

Results:

Participants reported 3648 new COPD diagnoses during follow-up. The incidence of COPD was higher in both severely obese (body mass index [BMI]D≥ 35) and underweight (BMID< 18.5) participants, but after adjustment for waist circumference, only underweight remained positively associated with COPD (relative risk [RR]D1.56, 95% confidence interval [CI]D1.15–2.11). Larger waist circumference (highest v. normal categories, adjusted RRD1.72, 95% CID1.37–2.16) and higher waist–hip ratio (highest v. normal categories, adjusted RRD1.46, 95% CID1.23–1.73) were also positively associated with COPD. In contrast, hip circumference (highest v. normal categories, adjusted RR 0.78, 95% CI 0.62–0.98) and physical activity (≥ 5 v. 0 times/wk, adjusted RRD0.71, 95% CID0.63–0.79) were inversely associated with COPD.

Interpretation:

Obesity, in particular abdominal adiposity, was associated with an increased risk of COPD, and increased hip circumference and physical activity were associated with a decreased risk of COPD. These findings suggest that following guidelines for a healthy body weight, body shape and physical activity decrease the risk of COPD.Chronic obstructive pulmonary disease (COPD) is a progressive, irreversible condition that severely affects quality of life¹ and ability to work.² Direct and indirect annual costs of COPD, including inpatient and outpatient care, medication and loss of productivity, sum to $50 billion in the United States³ and R39 billion (about US$50 billion) in Europe.⁴Chronic obstructive pulmonary disease may be prevented by avoidance of tobacco smoke, occupational dust and other environmental air pollution.⁵ Body mass index (BMI) and physical activity are established correlates of disease progression among patients with COPD,^6,7 but data relating body size or physical activity to incident COPD are sparse. The few studies available are based on small samples and show inverse relations of both BMI^8,9 and physical activity^10,11 to incidence of COPD. Data are lacking regarding waist or hip circumference in relation to COPD incidence. We therefore examined BMI, waist circumference, hip circumference, waist–hip ratio and physical activity in relation to incidence of COPD in a large cohort of women and men in the US.     

Oral administration of morphine versus ibuprofen to manage postfracture pain in children: a randomized trial

Background:

Recent warnings from Health Canada regarding codeine for children have led to increased use of nonsteroidal anti-inflammatory drugs and morphine for common injuries such as fractures. Our objective was to determine whether morphine administered orally has superior efficacy to ibuprofen in fracture-related pain.

Methods:

We used a parallel group, randomized, blinded superiority design. Children who presented to the emergency department with an uncomplicated extremity fracture were randomly assigned to receive either morphine (0.5 mg/kg orally) or ibuprofen (10 mg/kg) for 24 hours after discharge. Our primary outcome was the change in pain score using the Faces Pain Scale — Revised (FPS-R). Participants were asked to record pain scores immediately before and 30 minutes after receiving each dose.

Results:

We analyzed data from 66 participants in the morphine group and 68 participants in the ibuprofen group. For both morphine and ibuprofen, we found a reduction in pain scores (mean pre–post difference ± standard deviation for dose 1: morphine 1.5 ± 1.2, ibuprofen 1.3 ± 1.0, between-group difference [δ] 0.2 [95% confidence interval (CI) −0.2 to 0.6]; dose 2: morphine 1.3 ± 1.3, ibuprofen 1.3 ± 0.9, δ 0 [95% CI −0.4 to 0.4]; dose 3: morphine 1.3 ± 1.4, ibuprofen 1.4 ± 1.1, δ −0.1 [95% CI −0.7 to 0.4]; and dose 4: morphine 1.5 ± 1.4, ibuprofen 1.1 ± 1.2, δ 0.4 [95% CI −0.2 to 1.1]). We found no significant differences in the change in pain scores between morphine and ibuprofen between groups at any of the 4 time points (p = 0.6). Participants in the morphine group had significantly more adverse effects than those in the ibuprofen group (56.1% v. 30.9%, p < 0.01).

Interpretation:

We found no significant difference in analgesic efficacy between orally administered morphine and ibuprofen. However, morphine was associated with a significantly greater number of adverse effects. Our results suggest that ibuprofen remains safe and effective for outpatient pain management in children with uncomplicated fractures. Trial registration: ClinicalTrials.gov, no. {"type":"clinical-trial","attrs":{"text":"NCT01690780","term_id":"NCT01690780"}}NCT01690780.There is ample evidence that analgesia is underused,¹ underprescribed,² delayed in its administration² and suboptimally dosed ³ in clinical settings. Children are particularly susceptible to suboptimal pain management⁴ and are less likely to receive opioid analgesia.⁵ Untreated pain in childhood has been reported to lead to short-term problems such as slower healing⁶ and to long-term issues such as anxiety, needle phobia,⁷ hyperesthesia⁸ and fear of medical care.⁹ The American Academy of Pediatrics has reaffirmed its advocacy for the appropriate use of analgesia for children with acute pain.¹⁰Fractures constitute between 10% and 25% of all injuries.¹¹ The most severe pain after an injury occurs within the first 48 hours, with more than 80% of children showing compromise in at least 1 functional area.¹² Low rates of analgesia have been reported after discharge from hospital.¹³ A recently improved understanding of the pharmacogenomics of codeine has raised significant concerns about its safety,^14,15 and has led to a Food and Drug Administration boxed warning¹⁶ and a Health Canada advisory¹⁷ against its use. Although ibuprofen has been cited as the most common agent used by caregivers to treat musculoskeletal pain,^12,13 there are concerns that its use as monotherapy may lead to inadequate pain management.^6,18 Evidence suggests that orally administered morphine¹³ and other opioids are increasingly being prescribed.¹⁹ However, evidence for the oral administration of morphine in acute pain management is limited.^20,21 Thus, additional studies are needed to address this gap in knowledge and provide a scientific basis for outpatient analgesic choices in children. Our objective was to assess if orally administered morphine is superior to ibuprofen in relieving pain in children with nonoperative fractures.     

Child abuse and mental disorders in Canada

Background:

Nationally representative Canadian data on the prevalence of child abuse and its relation with mental disorders are lacking. We used contemporary, nationally representative data to examine the prevalence of 3 types of child abuse (physical abuse, sexual abuse and exposure to intimate partner violence) and their association with 14 mental conditions, including suicidal ideation and suicide attempts.

Methods:

We obtained data from the 2012 Canadian Community Health Survey: Mental Health, collected from the 10 provinces. Respondents aged 18 years and older were asked about child abuse and were selected for the study sample (n = 23 395). The survey had a multistage stratified cluster design (household response rate 79.8%).

Results:

The prevalence of any child abuse was 32% (individual types ranged from 8% to 26%). All types of child abuse were associated with all mental conditions, including suicidal ideation and suicide attempts, after adjustment for sociodemographic variables (adjusted odds ratios ranged from 1.4 to 7.9). We found a dose–response relation, with increasing number of abuse types experienced corresponding with greater odds of mental conditions. Associations between child abuse and attention deficit disorder, suicidal ideation and suicide attempts showed stronger effects for women than men.

Interpretation:

We found robust associations between child abuse and mental conditions. Health care providers, especially those assessing patients with mental health problems, need to be aware of the relation between specific types of child abuse and certain mental conditions. Success in preventing child abuse could lead to reductions in the prevalence of mental disorders, suicidal ideation and suicide attempts.Child abuse is a major public health problem worldwide with serious adverse effects at later ages. The best estimates of the prevalence of child abuse in Canada come from 2 representative samples from Ontario, 1 from 1990 (Ontario Health Supplement, n = 9953, age ≥ 15 yr)1 and 1 from 2000–2001 (Ontario Child Health Study, n = 1893, age 21–35 yr).² The 1990 study indicated that 31% of males and 21% of females had experienced physical child abuse, and 4% of males and 13% of females had experienced sexual child abuse.¹ Similar trends were noted in data collected in 2000–2001.² Prevalence of sexual abuse was found to be higher in the Ontario Child Health Study, but this was thought to be related to the inclusion of sexual abuse committed by anyone (e.g., adolescents), rather than only adults, as was the case with the Ontario Health Supplement.^1,2 Data from Quebec collected in 2006 indicated that 23% of men and 17% of women had experienced physical child abuse; 10% of men and 22% of women had experienced sexual child abuse; and 22% of men and women had experienced psychological child abuse, including exposure to intimate partner violence.^3,4 Unfortunately, these estimates are dated, restricted to only 2 provinces, based on limited assessments of child abuse and, in the case of the Quebec data, involve a low response rate of 30%.Although the association between child abuse and subsequent mental conditions (including disorders, suicidal ideation and suicide attempts) is well established,^5–9 we know little about differential effects associated with several abuse types and specific mental disorders, and we currently have no nationally representative Canadian data. Filling this gap in knowledge would produce evidence-based Canadian findings that could inform policy, prevention and intervention efforts specifically aimed at reducing both child abuse and poor mental health outcomes.Our overall objective was to extend our understanding of the relation between child abuse and mental conditions (i.e., mental disorders, suicidal ideation and suicide attempts)^{6–8,10–19} with a more detailed examination of child abuse severity and mental health outcomes. We used a nationally representative Canadian sample to examine 3 types of child abuse (physical abuse, sexual abuse and exposure to intimate partner violence) and 14 mental conditions, including suicidal ideation and suicide attempts. The specific research objectives were to estimate the prevalence of 3 types of physical abuse, sexual abuse and exposure to intimate partner violence; to examine the association of mental conditions with types of child abuse and number of child abuse types experienced; and to determine whether sex differences exist in the associations between child abuse and mental conditions.     

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.     

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.