A comparison of the stages at which cancer is diagnosed in physicians and in the general population in Taiwan

Background:Previous investigations have reported that physicians tend to neglect their own health care; however, they may also use their professional knowledge and networks to engage in healthier lifestyles or seek prompt health services. We sought to determine whether the stage at which cancer is diagnosed differs between physicians and nonphysicians.Methods:We conducted a nationwide matched cohort study over a period of 14 years in Taiwan. We accessed data from two national databases: the National Health Insurance Research Database and the Taiwan Cancer Registry File. We collected data on all patients with the 6 most common cancers in Taiwan (hepatoma, lung, colorectal, oral, female breast and cervical cancer) from 1999 to 2012. We excluded patients less than 25 years of age, as well as those with a history of organ transplantation, cancer or AIDS. We used propensity score matching for age, sex, residence and income to select members for the control (nonphysicians) and experimental (physicians) groups at a 5:1 ratio. We used χ² tests to analyze the distribution of incident cancer stages among physicians and nonphysicians. We compared these associations using multinomial logistic regression. We performed sensitivity analyses for subgroups of doctors and cancers.Results:We identified 274 003 patients with cancer, 542 of whom were physicians. After propensity score matching, we assigned 536 physicians to the experimental group and 2680 nonphysicians to the control group. We found no significant differences in cancer stage distributions between physicians and controls. Multinomial logistic regression and sensitivity analyses showed similar cancer stages in most scenarios; however, physicians had 2.64-fold higher risk of having stage IV cancer at diagnosis in cases of female breast and cervical cancer.Interpretation:In this cohort of physicians in Taiwan, cancer was not diagnosed at earlier stages than in nonphysicians, with the exception of stage IV cancer of the cervix and female breast.The health of physicians is vital to health care systems. Physicians who are unwell mentally or physically are prone to providing suboptimal patient care.¹ Several studies have investigated the risk of cancer for doctors with inconclusive findings;^1–4 few investigations have addressed whether cancer is diagnosed at earlier stages in physicians.Previous investigations have reported that physicians tend to neglect their own physical examinations and, once sick, procrastinate seeking medical treatment.^5–8 However, doctors may use their own professional knowledge and network to engage in healthy lifestyles or seek prompt health services in ways that reduce their risk of illness.^9–11Factors protecting people from advanced cancer stages include attending screening services^12–14 and access to physicians.^15,16 Delayed cancer diagnoses lead to poorer outcomes. We sought to compare the incident cancer stages of the 6 most common cancers between physicians and nonphysicians in Taiwan to determine whether physicians’ cancers were diagnosed at earlier or later stages than nonphysicians’ cancers.     

Effect of lung-protective ventilation with lower tidal volumes on clinical outcomes among patients undergoing surgery: a meta-analysis of randomized controlled trials

Background:In anesthetized patients undergoing surgery, the role of lung-protective ventilation with lower tidal volumes is unclear. We performed a meta-analysis of randomized controlled trials (RCTs) to evaluate the effect of this ventilation strategy on postoperative outcomes.Methods:We searched electronic databases from inception through September 2014. We included RCTs that compared protective ventilation with lower tidal volumes and conventional ventilation with higher tidal volumes in anesthetized adults undergoing surgery. We pooled outcomes using a random-effects model. The primary outcome measures were lung injury and pulmonary infection.Results:We included 19 trials (n = 1348). Compared with patients in the control group, those who received lung-protective ventilation had a decreased risk of lung injury (risk ratio [RR] 0.36, 95% confidence interval [CI] 0.17 to 0.78; I² = 0%) and pulmonary infection (RR 0.46, 95% CI 0.26 to 0.83; I² = 8%), and higher levels of arterial partial pressure of carbon dioxide (standardized mean difference 0.47, 95% CI 0.18 to 0.75; I² = 65%). No significant differences were observed between the patient groups in atelectasis, mortality, length of hospital stay, length of stay in the intensive care unit or the ratio of arterial partial pressure of oxygen to fraction of inspired oxygen.Interpretation:Anesthetized patients who received ventilation with lower tidal volumes during surgery had a lower risk of lung injury and pulmonary infection than those given conventional ventilation with higher tidal volumes. Implementation of a lung-protective ventilation strategy with lower tidal volumes may lower the incidence of these outcomes.Estimates suggest that more than 230 million patients undergo major surgical procedures worldwide each year.¹ Postoperative pulmonary complications, including lung injury, pneumonia and atelectasis, are common and a major cause of morbidity and death.^2–5 Thus, prevention of these complications has become a high priority of perioperative care.Mechanical ventilation is mandatory in patients undergoing surgical procedures during general anesthesia. Conventional mechanical ventilation with tidal volumes of 10 to 15 mL/kg has been advocated to prevent hypoxemia and atelectasis in anesthetized patients undergoing surgery.⁶ However, unequivocal evidence from experimental and clinical studies suggests that mechanical ventilation, especially the use of high tidal volumes, may cause or aggravate lung injury.^7–9 Mechanical ventilation using high tidal volumes can result in overdistention of alveoli that mainly causes ventilator-associated lung injury.¹⁰Lung-protective ventilation refers to the use of low tidal volumes and moderate to high levels of positive end-expiratory pressure, with or without a recruitment manoeuvre.¹¹ Lung-protective ventilation has been found to reduce morbidity and mortality among patients with acute lung injury and acute respiratory distress syndrome.^11,12 However, in anesthetized patients without the syndrome, the role of lung-protective ventilation remains unclear. Two previous meta-analyses addressing similar research questions have been published,^13,14 but the inclusion of observational studies compromised the reliability of the results. Recently, randomized controlled trials (RCTs) on the topic have reported conflicting results. We performed a meta-analysis of RCTs to evaluate the effect of lung-protective ventilation with lower tidal volumes on clinical outcomes in patients undergoing surgery.     

Determinants of variations in initial treatment strategies for stable ischemic heart disease

Background:

The ratio of revascularization to medical therapy (referred to herein as the revascularization ratio) for the initial treatment of stable ischemic heart disease varies considerably across hospitals. We conducted a comprehensive study to identify patient, physician and hospital factors associated with variations in the revascularization ratio across 18 cardiac centres in the province of Ontario. We also explored whether clinical outcomes differed between hospitals with high, medium and low ratios.

Methods:

We identified all patients in Ontario who had stable ischemic heart disease documented by index angiography performed between Oct. 1, 2008, and Sept. 30, 2011, at any of the 18 cardiac centres in the province. We classified patients by initial treatment strategy (medical therapy or revascularization). Hospitals were classified into equal tertiles based on their revascularization ratio. The primary outcome was all-cause mortality. Patient follow-up was until Dec. 31, 2012. Hierarchical logistic regression models identified predictors of revascularization. Multivariable Cox proportional hazards models, with a time-varying covariate for actual treatment received, were used to evaluate the impact of the revascularization ratio on clinical outcomes.

Results:

Variation in revascularization ratios was twofold across the hospitals. Patient factors accounted for 67.4% of the variation in revascularization ratios. Physician and hospital factors were not significantly associated with the variation. Significant patient-level predictors of revascularization were history of smoking, multivessel disease, high-risk findings on noninvasive stress testing and more severe symptoms of angina (v. no symptoms). Treatment at hospitals with a high revascularization ratio was associated with increased mortality compared with treatment at hospitals with a low ratio (hazard ratio 1.12, 95% confidence interval 1.03–1.21).

Interpretation:

Most of the variation in revascularization ratios across hospitals was warranted, in that it was driven by patient factors. Nonetheless, the variation was associated with potentially important differences in mortality.Stable ischemic heart disease is a common manifestation of cardiovascular disease, the leading cause of death in the world.^1,2 The treatment strategies for stable ischemic heart disease include medical therapy alone or in combination with revascularization by percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG).A tremendous amount of research has examined the best initial treatment strategy for stable ischemic heart disease.^3–5 Randomized controlled trials have not shown a difference in major adverse events between optimal medical therapy and revascularization.⁶ Some argue that revascularization should be reserved only for symptom relief.^5,7,8 Criteria for the appropriate use of revascularization have been developed to aid in clinical decision-making; however, a substantial proportion of revascularization procedures for stable ischemic heart disease are performed under clinical circumstances deemed as “uncertain.”^9,10 Reflecting this uncertainty, there is wide regional variation in the rate of coronary revascularization,^11–13 which suggests different thresholds for invasive therapy for stable ischemic heart disease.Studies have predominantly examined the determinants of variations in the type of revascularization modality used.^13,14 There is a paucity of data exploring the determinants of variations in the earlier decision to treat with medical therapy alone or with revascularization. A study published nearly a decade ago did not examine outcomes.⁷ Accordingly, our primary research objective was to determine whether the variations in initial treatment strategies for stable ischemic heart disease are warranted. We conducted a comprehensive population-based study to identify patient, physician and hospital factors associated with variations in treatment strategies within 90 days after angiography. We also explored whether clinical outcomes differed between hospitals with high, medium and low ratios of revascularization to medical therapy (hereafter referred to as the revascularization ratio).     

Longitudinal evaluation of physician payment reform and team-based care for chronic disease management and prevention

Background:

We evaluated a large-scale transition of primary care physicians to blended capitation models and team-based care in Ontario, Canada, to understand the effect of each type of reform on the management and prevention of chronic disease.

Methods:

We used population-based administrative data to assess monitoring of diabetes mellitus and screening for cervical, breast and colorectal cancer among patients belonging to team-based capitation, non–team-based capitation or enhanced fee-for-service medical homes as of Mar. 31, 2011 (n = 10 675 480). We used Poisson regression models to examine these associations for 2011. We then used a fitted nonlinear model to compare changes in outcomes between 2001 and 2011 by type of medical home.

Results:

In 2011, patients in a team-based capitation setting were more likely than those in an enhanced fee-for-service setting to receive diabetes monitoring (39.7% v. 31.6%, adjusted relative risk [RR] 1.22, 95% confidence interval [CI] 1.18 to 1.25), mammography (76.6% v. 71.5%, adjusted RR 1.06, 95% CI 1.06 to 1.07) and colorectal cancer screening (63.0% v. 60.9%, adjusted RR 1.03, 95% CI 1.02 to 1.04). Over time, patients in medical homes with team-based capitation experienced the greatest improvement in diabetes monitoring (absolute difference in improvement 10.6% [95% CI 7.9% to 13.2%] compared with enhanced fee for service; 6.4% [95% CI 3.8% to 9.1%] compared with non–team-based capitation) and cervical cancer screening (absolute difference in improvement 7.0% [95% CI 5.5% to 8.5%] compared with enhanced fee for service; 5.3% [95% CI 3.8% to 6.8%] compared with non–team-based capitation). For breast and colorectal cancer screening, there were no significant differences in change over time between different types of medical homes.

Interpretation:

The shift to capitation payment and the addition of team-based care in Ontario were associated with moderate improvements in processes related to diabetes care, but the effects on cancer screening were less clear.Health care systems with a strong primary care orientation have better health outcomes, lower costs and fewer disparities across population subgroups.¹ Countries around the world have been experimenting with reforms to improve the delivery of primary care, changing the way physicians are organized and paid. In the United States, several national organizations^2,3 and policy experts^4,5 have advocated a shift away from fee for service toward capitation or blended payments, and in 2015, the Centers for Medicare and Medicaid Services brought in blended payment in primary care, introducing a non–visit-based payment for chronic care management.⁶Patient-centred medical homes have provided an opportunity to transition physicians to new payment models, but they also necessitate changes in care delivery, including incorporation of team-based care, enhancement of access for patients, coordination of care and a focus on quality and safety.^7–9 Evidence suggests that team-based care is a particularly important element in improving the management and prevention of chronic disease and reducing related costs.¹⁰ Early evaluations of patient-centred medical home pilots were promising,^11,12 but a recent study of large-scale implementation showed limited improvements in the quality of chronic disease care and no reduction in health care utilization or total costs over 3 years.¹³Before 2002, primary care physicians in Ontario, Canada, were almost universally paid through a fee-for-service system. Over the past decade, more than three-quarters have transitioned to patient-centred medical homes.^14,15 About half of Ontario physicians working in patient-centred medical homes have shifted to blended capitation payments, with a portion of these physicians working in groups that also receive government funding for nonphysician health professionals to enable team-based care. However, about 40% of physicians in patient-centred medical homes still receive most of their income through fee-for-service payments. This natural health policy experiment offers a unique opportunity to compare the effectiveness of different payment models and team-based care. Early studies have shown small differences in the quality of cardiovascular¹⁶ and diabetes mellitus¹⁷ care between physicians receiving capitation payments and those receiving fee-for-service payments, but no studies have assessed changes in quality of care over time.We evaluated a large-scale transition of primary care physicians to blended capitation models and team-based care to understand the effect of each type of reform on chronic disease management and prevention over time.     

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.     

Imaging for distant metastases in women with early-stage breast cancer: a population-based cohort study

Background:

Practice guidelines recommend that imaging to detect metastatic disease not be performed in the majority of patients with early-stage breast cancer who are asymptomatic. We aimed to determine whether practice patterns in Ontario conform with these recommendations.

Methods:

We used provincial registry data to identify a population-based cohort of Ontario women in whom early-stage, operable breast cancer was diagnosed between 2007 and 2012. We then determined whether imaging of the skeleton, thorax, and abdomen or pelvis had been performed within 3 months of tissue diagnosis. We calculated rates of confirmatory imaging of the same body site.

Results:

Of 26 547 patients with early-stage disease, 22 811 (85.9%) had at least one imaging test, and a total of 83 249 imaging tests were performed (mean of 3.7 imaging tests per patient imaged). Among patients with pathologic stage I and II disease, imaging was performed in 79.6% (10 921/13 724) and 92.7% (11 882/12 823) of cases, respectively. Of all imaging tests, 19 784 (23.8%) were classified as confirmatory investigations. Imaging was more likely for patients who were younger, had greater comorbidity, had tumours of higher grade or stage or had undergone preoperative breast ultrasonography, mastectomy or surgery in the community setting.

Interpretation:

Despite recommendations from multiple international guidelines, most Ontario women with early-stage breast cancer underwent imaging to detect distant metastases. Inappropriate imaging in asymptomatic patients with early-stage disease is costly and may lead to harm. The use of population datasets will allow investigators to evaluate whether or not strategies to implement practice guidelines lead to meaningful and sustained change in physician practice.Most women with newly diagnosed breast cancer present with early-stage, potentially curable disease.¹ Among patients whose disease is restricted to the breast and axillary lymph nodes, without signs or symptoms of metastatic disease, the likelihood of having radiologically evident metastases in pathologic stage I and II disease is about 0.2% and 1.2%, respectively.² This low frequency has not changed significantly, even with the increasing use of magnetic resonance imaging (MRI) and positron emission tomography.^2,3 For this reason, most provincial, national and international guidelines do not recommend imaging for all patients with early-stage breast cancer who are asymptomatic.^4–8Despite these evidence-based guidelines, imaging for distant metastases in patients with a new diagnosis of breast cancer remains common.^2,9–12 In response to the Choosing Wisely campaign of the American Board of Internal Medicine Foundation,¹³ the American Society of Clinical Oncology (ASCO) published its inaugural “top 5” list for choosing wisely in oncology.¹⁴ It recommended against routine imaging for staging purposes in women with early breast cancer, because “such imaging adds little benefit to patient care and has the potential to cause harm.”¹⁴ In 2014, Choosing Wisely Canada was launched in an effort to encourage physicians and patients to engage in conversations about unnecessary tests, treatments and procedures, to help ensure that patients receive the highest-quality care.¹⁵The ASCO Choosing Wisely recommendation¹⁴ is similar to the Cancer Care Ontario guideline,⁴ which has been in existence for over a decade. Whereas ASCO in its Choosing Wisely campaign recommends no imaging for patients with stage I or II disease, the Cancer Care Ontario guideline recommends no imaging for patients with stage I disease and a bone scan for those with stage II disease. A recent study at a large Canadian academic cancer centre showed that, despite publication of both a provincial guideline and the ASCO recommendations, most patients with primary operable (early-stage) breast cancer undergo imaging for distant metastases.¹⁰ We hypothesized that despite the provincial guideline, this practice may be more widespread. We undertook this population-based study to determine whether physician practice patterns in Ontario regarding imaging of patients with early-stage breast cancer are in keeping with the published Cancer Care Ontario guideline.     

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.     

Prevalence of and risk factors for persistent postoperative nonanginal pain after cardiac surgery: a 2-year prospective multicentre study

Background:

Persistent postoperative pain continues to be an underrecognized complication. We examined the prevalence of and risk factors for this type of pain after cardiac surgery.

Methods:

We enrolled patients scheduled for coronary artery bypass grafting or valve replacement, or both, from Feb. 8, 2005, to Sept. 1, 2009. Validated measures were used to assess (a) preoperative anxiety and depression, tendency to catastrophize in the face of pain, health-related quality of life and presence of persistent pain; (b) pain intensity and interference in the first postoperative week; and (c) presence and intensity of persistent postoperative pain at 3, 6, 12 and 24 months after surgery. The primary outcome was the presence of persistent postoperative pain during 24 months of follow-up.

Results:

A total of 1247 patients completed the preoperative assessment. Follow-up retention rates at 3 and 24 months were 84% and 78%, respectively. The prevalence of persistent postoperative pain decreased significantly over time, from 40.1% at 3 months to 22.1% at 6 months, 16.5% at 12 months and 9.5% at 24 months; the pain was rated as moderate to severe in 3.6% at 24 months. Acute postoperative pain predicted both the presence and severity of persistent postoperative pain. The more intense the pain during the first week after surgery and the more it interfered with functioning, the more likely the patients were to report persistent postoperative pain. Pre-existing persistent pain and increased preoperative anxiety also predicted the presence of persistent postoperative pain.

Interpretation:

Persistent postoperative pain of nonanginal origin after cardiac surgery affected a substantial proportion of the study population. Future research is needed to determine whether interventions to modify certain risk factors, such as preoperative anxiety and the severity of pain before and immediately after surgery, may help to minimize or prevent persistent postoperative pain.Postoperative pain that persists beyond the normal time for tissue healing (> 3 mo) is increasingly recognized as an important complication after various types of surgery and can have serious consequences on patients’ daily living.^1–3 Cardiac surgeries, such as coronary artery bypass grafting (CABG) and valve replacement, rank among the most frequently performed interventions worldwide.⁴ They aim to improve survival and quality of life by reducing symptoms, including anginal pain. However, persistent postoperative pain of nonanginal origin has been reported in 7% to 60% of patients following these surgeries.^5–23 Such variability is common in other types of major surgery and is due mainly to differences in the definition of persistent postoperative pain, study design, data collection methods and duration of follow-up.^1–3,24Few prospective cohort studies have examined the exact time course of persistent postoperative pain after cardiac surgery, and follow-up has always been limited to a year or less.^9,14,25 Factors that put patients at risk of this type of problem are poorly understood.²⁶ Studies have reported inconsistent results regarding the contribution of age, sex, body mass index, preoperative angina, surgical technique, grafting site, postoperative complications or level of opioid consumption after surgery.^{5–7,9,13,14,16–19,21–23,25,27} Only 1 study investigated the role of chronic nonanginal pain before surgery as a contributing factor;²¹ 5 others prospectively assessed the association between persistent postoperative pain and acute pain intensity in the first postoperative week but reported conflicting results.^{13,14,21,22,25} All of the above studies were carried out in a single hospital and included relatively small samples. None of the studies examined the contribution of psychological factors such as levels of anxiety and depression before cardiac surgery, although these factors have been shown to influence acute or persistent postoperative pain in other types of surgery.^1,24,28,29We conducted a prospective multicentre cohort study (the CARD-PAIN study) to determine the prevalence of persistent postoperative pain of nonanginal origin up to 24 months after cardiac surgery and to identify risk factors for the presence and severity of the condition.     

Prospective validation of a 1-hour algorithm to rule-out and rule-in acute myocardial infarction using a high-sensitivity cardiac troponin T assay

Background:We aimed to prospectively validate a novel 1-hour algorithm using high-sensitivity cardiac troponin T measurement for early rule-out and rule-in of acute myocardial infarction (MI).Methods:In a multicentre study, we enrolled 1320 patients presenting to the emergency department with suspected acute MI. The high-sensitivity cardiac troponin T 1-hour algorithm, incorporating baseline values as well as absolute changes within the first hour, was validated against the final diagnosis. The final diagnosis was then adjudicated by 2 independent cardiologists using all available information, including coronary angiography, echocardiography, follow-up data and serial measurements of high-sensitivity cardiac troponin T levels.Results:Acute MI was the final diagnosis in 17.3% of patients. With application of the high-sensitivity cardiac troponin T 1-hour algorithm, 786 (59.5%) patients were classified as “rule-out,” 216 (16.4%) were classified as “rule-in” and 318 (24.1%) were classified to the “observational zone.” The sensitivity and the negative predictive value for acute MI in the rule-out zone were 99.6% (95% confidence interval [CI] 97.6%–99.9%) and 99.9% (95% CI 99.3%–100%), respectively. The specificity and the positive predictive value for acute MI in the rule-in zone were 95.7% (95% CI 94.3%–96.8%) and 78.2% (95% CI 72.1%–83.6%), respectively. The 1-hour algorithm provided higher negative and positive predictive values than the standard interpretation of highsensitivity cardiac troponin T using a single cut-off level (both p < 0.05). Cumulative 30-day mortality was 0.0%, 1.6% and 1.9% in patients classified in the rule-out, observational and rule-in groups, respectively (p = 0.001).Interpretation:This rapid strategy incorporating high-sensitivity cardiac troponin T baseline values and absolute changes within the first hour substantially accelerated the management of suspected acute MI by allowing safe rule-out as well as accurate rule-in of acute MI in 3 out of 4 patients. Trial registration: ClinicalTrials.gov, {"type":"clinical-trial","attrs":{"text":"NCT00470587","term_id":"NCT00470587"}}NCT00470587Acute myocardial infarction (MI) is a major cause of death and disability worldwide. As highly effective treatments are available, early and accurate detection of acute MI is crucial.^1–5 Clinical assessment, 12-lead electrocardiography (ECG) and measurement of cardiac troponin levels form the pillars for the early diagnosis of acute MI in the emergency department. Major advances have recently been achieved by the development of more sensitive cardiac troponin assays.^6–15 High-sensitivity cardiac troponin assays, which allow measurement of even low concentrations of cardiac troponin with high precision, have been shown to largely overcome the sensitivity deficit of conventional cardiac troponin assays within the first hours of presentation in the diagnosis of acute MI.^6–15 These studies have consistently shown that the classic diagnostic interpretation of cardiac troponin as a dichotomous variable (troponin-negative and troponin-positive) no longer seems appropriate, because the positive predictive value for acute MI of being troponin-positive was only about 50%.^6–15 The best way to interpret and clinically use high-sensitivity cardiac troponin levels in the early diagnosis of acute MI is still debated.^3,5,7In a pilot study, a novel high-sensitivity cardiac troponin T 1-hour algorithm was shown to allow accurate rule-out and rule-in of acute MI within 1 hour in up to 75% of patients.¹¹ This algorithm is based on 2 concepts. First, high-sensitivity cardiac troponin T is interpreted as a quantitative variable where the proportion of patients who have acute MI increases with increasing concentrations of cardiac troponin T.^6–15 Second, early absolute changes in the concentrations within 1 hour provide incremental diagnostic information when added to baseline levels, with the combination acting as a reliable surrogate for late concentrations at 3 or 6 hours.^6–15 However, many experts remained skeptical regarding the safety of the high-sensitivity cardiac troponin T 1-hour algorithm and its wider applicability.¹⁶ Accordingly, this novel diagnostic concept has not been adopted clinically to date. Because the clinical application of this algorithm would represent a profound change in clinical practice, prospective validation in a large cohort is mandatory before it can be considered for routine clinical use. The aim of this multicentre study was to prospectively validate the high-sensitivity cardiac troponin T 1-hour algorithm in a large independent cohort.     

Incidence of psychotic disorders among first-generation immigrants and refugees in Ontario

Background:

Evidence suggests that migrant groups have an increased risk of psychotic disorders and that the level of risk varies by country of origin and host country. Canadian evidence is lacking on the incidence of psychotic disorders among migrants. We sought to examine the incidence of schizophrenia and schizoaffective disorders in first-generation immigrants and refugees in the province of Ontario, relative to the general population.

Methods:

We constructed a retrospective cohort that included people aged 14–40 years residing in Ontario as of Apr. 1, 1999. Population-based administrative data from physician billings and hospital admissions were linked to data from Citizenship and Immigration Canada. We used Poisson regression models to calculate age- and sex-adjusted incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for immigrant and refugee groups over a 10-year period.

Results:

In our cohort (n = 4 284 694), we found higher rates of psychotic disorders among immigrants from the Caribbean and Bermuda (IRR 1.60, 95% CI 1.29–1.98). Lower rates were found among immigrants from northern Europe (IRR 0.50, 95% CI 0.28–0.91), southern Europe (IRR 0.60, 95% CI 0.41–0.90) and East Asia (IRR 0.56, 95% CI 0.41–0.78). Refugee status was an independent predictor of risk among all migrants (IRR 1.27, 95% CI 1.04–1.56), and higher rates were found specifically for refugees from East Africa (IRR 1.95, 95% CI 1.44–2.65) and South Asia (IRR 1.51, 95% CI 1.08–2.12).

Interpretation:

The differential pattern of risk across ethnic subgroups in Ontario suggests that psychosocial and cultural factors associated with migration may contribute to the risk of psychotic disorders. Some groups may be more at risk, whereas others are protected.Meta-analytic reviews suggest that international migrants have a two- to threefold increased risk of psychosis compared with the host population, and the level of risk varies by country of origin and host country.^1,2 This increased risk may persist into the second and third generations.^2,3 Incidence rates are not typically found to be elevated in the country of origin;^4–7 therefore, it is believed that the migratory or postmigration experience may play a role in the etiology.The migration-related emergence of psychotic disorders is a potential concern in Canada, which receives about 250 000 new immigrants and refugees each year.⁸ However, there is a notable lack of current epidemiological information on the incidence of psychosis among these groups.⁹ Hospital admission data from the early 1900s suggest that European migrants to British Columbia had a higher incidence of schizophrenia than the general population,¹⁰ and more recent data from Ontario suggest higher rates of hospital admission for psychotic disorders in areas with a large proportion of first-generation migrants.¹¹ The fact that a large and increasing proportion of Canada’s population are migrants has been cited as a potential explanation for the higher prevalence of schizophrenia compared with international estimates.¹²The province of Ontario is home to the largest number of migrants in Canada, with first-generation migrants constituting nearly 30% of the population. Canada operates on a human capital model of immigration, using a points-based system that favours younger age, higher education, and proficiency in English or French. Nearly 60% of all newcomers to Canada are economic migrants, 27% are sponsored by a relative living in Canada, and 13% are refugees or temporary workers.⁸ Canada also requires a prearrival medical examination, but less than 0.001% of all applications are denied on the basis of medical grounds, and exemptions may be granted for refugees and some family-reunification applicants.¹³The Canadian migration process differs from that of many countries where the association between migration and psychotic disorders has been previously investigated.^1,2 In most of these countries, migrants generally originate from a smaller number of countries that have historic ties to the host country, and there tends to be a low proportion of refugees, although these processes have changed in recent years. In Canada, migrants come from a wide array of countries, admission policies focus on migrants with professional skills and there is a larger proportion of refugees. Few studies to date have examined the role of refugee status in the risk of psychotic disorders¹⁴ or have assessed all of the migrant groups within a country, because most studies focus on particular groups considered to be at high risk.¹ An examination of migrants to Canada offers a unique opportunity to investigate the risk of psychotic disorders in a group with diverse geographical origins, and the larger proportion of refugees also allows us to investigate their risk separately from immigrant groups. Thus, the breadth, scope and scale of migration to Canada over time offers a diverse and deep population for advancing our understanding of why some groups may have a higher risk of psychotic disorders.Our primary objective was to examine the incidence of schizophrenia and schizoaffective disorders over a 10-year period in first-generation immigrants and refugees in Ontario, relative to the general population. We also compared the incidence among specific migrant groups, stratified by country of birth and refugee status, because research suggests differences in the degree and direction of risk.^1,2 We restricted the sample to first-generation migrants to estimate the extent to which sociodemographic factors had an impact on the risk of schizophrenia and schizoaffective disorders among all migrants.     

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.     

Development of guidelines for recently arrived immigrants and refugees to Canada: Delphi consensus on selecting preventable and treatable conditions

Background:

Setting priorities is critical to ensure guidelines are relevant and acceptable to users, and that time, resources and expertise are used cost-effectively in their development. Stakeholder engagement and the use of an explicit procedure for developing recommendations are critical components in this process.

Methods:

We used a modified Delphi consensus process to select 20 high-priority conditions for guideline development. Canadian primary care practitioners who care for immigrants and refugees used criteria that emphasize inequities in health to identify clinical care gaps.

Results:

Nine infectious diseases were selected, as well as four mental health conditions, three maternal and child health issues, caries and periodontal disease, iron-deficiency anemia, diabetes and vision screening.

Interpretation:

Immigrant and refugee medicine covers the full spectrum of primary care, and although infectious disease continues to be an important area of concern, we are now seeing mental health and chronic diseases as key considerations for recently arriving immigrants and refugees.Canada consistently receives more than 239 000 immigrants yearly, up to 35 000 of whom are refugees.¹ Many arrive with similar or better self-reported health than the general Canadian population reports, a phenomenon described as the “healthy immigrant effect.”^2–6 However, subgroups of immigrants, for example refugees, face health disparities and often a greater burden of infectious diseases.^7,8 These health issues sometimes differ from the general population because of differing disease exposures, vulnerabilities, social determinants of health and access to health services before, during and after migration. Cultural and linguistic differences combined with lack of evidence-based guidelines can contribute to poor delivery of services.^9,10Community-based primary health care practitioners see most of the immigrants and refugees who arrive in Canada. This is not only because Canada’s health system centres on primary care practice, but also because people with lower socioeconomic status, language barriers and less familiarity with the system are much less likely to receive specialist care.¹¹Guideline development can be costly in terms of time, resources and expertise.¹² Setting priorities is critical, particularly when dealing with complex situations and limited resources.¹³ There is no standard algorithm on who should and how they should determine top priorities for guidelines, although burden of illness, feasibility and economic considerations are all important.¹⁴ Stakeholder engagement to ensure relevance and acceptability, and the use of an explicit procedure for developing recommendations are critical in guideline development.^15–17 We chose primary care practitioners, particularly those who care for immigrants and refugees, to help the guideline committee select conditions for clinical preventive guidelines for immigrants and refugees with a focus on the first five years of settlement.     

Trends in suicidal behaviour and use of mental health services in Canadian military and civilian populations

Background:In the context of the Canadian mission in Afghanistan, substantial media attention has been placed on mental health and lack of access to treatment among Canadian Forces personnel. We compared trends in the prevalence of suicidal behaviour and the use of mental health services between Canadian military personnel and the general population from 2002 to 2012/13.Methods:We obtained data for respondents aged 18–60 years who participated in 4 nationally representative surveys by Statistics Canada designed to permit comparisons between populations and trends over time. Surveys of the general population were conducted in 2002 (n = 25 643) and 2012 (n = 15 981); those of military personnel were conducted in 2002 (n = 5153) and 2013 (n = 6700). We assessed the lifetime and past-year prevalence of suicidal ideation, plans and attempts, as well as use of mental health services.Results:In 2012/13, but not in 2002, military personnel had significantly higher odds of both lifetime and past-year suicidal ideation than the civilian population (lifetime: adjusted odds ratio [OR] 1.32, 95% confidence interval [CI] 1.17–1.50; past year: adjusted OR 1.34, 95% CI 1.09–1.66). The same was true for suicidal plans (lifetime: adjusted OR 1.64, 95% CI 1.35–1.99; past year: adjusted OR 1.66, 95% CI 1.18–2.33). Among respondents who reported past-year suicidal ideation, those in the military had a significantly higher past-year utilization rate of mental health services than those in the civilian population in both 2002 (adjusted OR 2.02, 95% CI 1.31–3.13) and 2012/13 (adjusted OR 3.14, 95% CI 1.86–5.28).Interpretation:Canadian Forces personnel had a higher prevalence of suicidal ideation and plans in 2012/13 and a higher use of mental health services in 2002 and 2012/13 than the civilian population.Suicide is a leading cause of death around the world in military and civilian populations. ^1–3 There has been increased attention paid to suicidal behaviour in Canada, and a number of initiatives are being put in place to prevent suicide through better recognition and treatment of mental disorders.⁴ Examples of major Canadian initiatives include creation of a national Mental Health Commission of Canada,⁵ development of a federal framework for suicide prevention,⁶ large investments in military and veteran mental health services, and targeted efforts to formulate comprehensive suicide prevention strategies among military and veteran populations.^4,7 Despite these initiatives, the prevalence of suicide in Canada has not changed appreciably in recent years.^8,9A recent report on suicides in the Canadian Forces did not find an overall increase in the prevalence of suicide between 1995 and 2014.¹⁰ However, the prevalence increased substantially over that time in the subgroup of male army personnel in the Regular Force.¹⁰ In the United States, the army has observed steady increases in the prevalence of suicide attempts and completed suicide by soldiers since 2004, whereas the prevalence of suicide has remained unchanged in the general population.^3,11,12 Findings from the US are not generalizable to the Canadian military because of differences in recruitment, deployment policies and health care systems.¹³Suicidal ideation, plans and attempts are strong risk factors for death by suicide.¹⁴ A history of suicide attempt is the strongest predictor of future attempts.¹⁵ Suicidal ideation is also an important target for intervention because previous work has shown a rapid transition from first-onset suicidal ideation to plans and attempts within the same year.¹⁶ It remains unknown whether nonfatal suicidal behaviour in military and civilian populations in Canada has changed over time.Another area of major public health concern is that most people with suicidal behaviour do not receive mental health services. In nationally representative civilian samples in Canada and 21 other countries, most respondents with suicidal behaviours (60%) did not receive mental health services. ^17,18 The use of such services among Canadian military personnel with suicidal behaviours remains unknown. The media has recently been critical of the Canadian Armed Forces and Veterans Affairs Canada about insufficient services available to military personnel and veterans.¹⁹We compared trends in the prevalence of suicidal behaviours and help-seeking between Canadian civilian and military populations over a 10-year period from 2002 to 2012/13 using data from 4 nationally representative surveys.     

Societal preferences for the return of incidental findings from clinical genomic sequencing: a discrete-choice experiment

Background:An important challenge with the application of next-generation sequencing technology is the possibility of uncovering incidental genomic findings. A paucity of evidence on personal utility for incidental findings has hindered clinical guidelines. Our objective was to estimate personal utility for complex information derived from incidental genomic findings.Methods:We used a discrete-choice experiment to evaluate participants’ personal utility for the following attributes: disease penetrance, disease treatability, disease severity, carrier status and cost. Study participants were drawn from the Canadian public. We analyzed the data with a mixed logit model.Results:In total, 1200 participants completed our questionnaire (available in English and French). Participants valued receiving information about high-penetrance disorders but expressed disutility for receiving information on low-penetrance disorders. The average willingness to pay was $445 (95% confidence interval [CI] $322–$567) to receive incidental findings in a scenario where clinicians returned information about high-penetrance, medically treatable disorders, but only 66% of participants (95% CI 63%–71%) indicated that they would choose to receive information in that scenario. On average, participants placed an important value ($725, 95% CI $600–$850) on having a choice about what type of findings they would receive, including receipt of information about high-penetrance, treatable disorders or receipt of information about high-penetrance disorders with or without available treatment. The predicted uptake of that scenario was 76% (95% CI 72%–79%).Interpretation:Most participants valued receiving incidental findings, but personal utility depended on the type of finding, and not all participants wanted to receive incidental results, regardless of the potential health implications. These results indicate that to maximize benefit, participant-level preferences should inform the decision about whether to return incidental findings.Clinical genomic sequencing technologies are on the verge of allowing individualized care at reasonable cost.¹ Patients and their families will soon receive information from clinical sequencing that has implications for clinical care, including information on consequences related to disease prognosis, treatment response or hereditary risk for disease.² Clinical sequencing can also generate incidental findings, which are clinically relevant genetic variants for disorders unrelated to the reason for ordering the genetic testing. The decision of whether to provide information about incidental findings is complex because such results will have varying clinical validity (whether the genetic variant causes the disorder) and utility (whether effective medical treatment is available for the disorder).^3,4 For example, although effective medical treatment may be available for some validated incidental findings, other incidental findings may not be validated as causing the disorder, and still others will be validated but not associated with effective treatment options.To address in part the challenges surrounding the return of incidental findings, the American College of Medical Genetics and Genomics published recommendations for reporting incidental findings from clinical sequencing.⁵ The statement lists a minimum of 56 genes that laboratories should examine, with results reported to patients through the managing physician. This list includes genes with high-penetrance mutations (i.e., a high proportion of individuals with the mutation will exhibit clinical symptoms) validated to be associated with disorders for which medical interventions are available.The original version of this statement did not “favour offering the patient a preference” for which results would be returned. The reasoning was that clinicians have a duty to prevent potential harm by telling patients about incidental findings. The working group that developed the recommendations further stated that it is impractical to provide the level of genetic counselling required for informed preference on all potential disorders.⁵ As such, the working group recommended that clinicians discuss with patients the possibility of receiving incidental findings from the list. It was argued that patient autonomy is preserved because patients can decline clinical sequencing if they prefer to not receive information about incidental findings.⁵ However, this rationale has been subject to debate because of its “all-or-none” nature, whereby patients must agree to receive information about incidental findings or clinical sequencing is not provided.^6–9 In April 2014, in response to the ongoing debate, the statement was amended to include an “opt-out” option for patients who do not want to receive information about incidental findings.¹⁰Notwithstanding the ethical debate, there is a lack of quantitative, preference-based economic evidence for the return of incidental genomic findings.⁸ It has been argued⁸ that this gap in evidence hindered development of the working group’s recommendation statement. More generally, evidence on preferences for the return of incidental findings is crucial for health policy, for health systems planning and for informing future lists that may include “many more genes.”⁸ We aimed to generate evidence on the personal utility that study participants from the Canadian public ascribe to the return of incidental genomic findings in the clinical setting. We chose participants from the general public because the public is the largest stakeholder in Canada’s publicly funded health care system.     

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.     

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.