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.     

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.     

Higher risk of venous thrombosis associated with drospirenone-containing oral contraceptives: a population-based cohort study

Background:

Combined oral contraceptives are a common method of contraception, but they carry a risk of venous and arterial thrombosis. We assessed whether use of drospirenone was associated with an increase in thrombotic risk relative to third-generation combined oral contraceptives.

Methods:

Using computerized records of the largest health care provider in Israel, we identified all women aged 12 to 50 years for whom combined oral contraceptives had been dispensed between Jan. 1, 2002, and Dec. 31, 2008. We followed the cohort until 2009. We used Poisson regression models to estimate the crude and adjusted rate ratios for risk factors for venous thrombotic events (specifically deep vein thrombosis and pulmonary embolism) and arterial thromboic events (specifically transient ischemic attack and cerebrovascular accident). We performed multivariable analyses to compare types of contraceptives, with adjustment for the various risk factors.

Results:

We identified a total of 1017 (0.24%) venous and arterial thrombotic events among 431 223 use episodes during 819 749 woman-years of follow-up (6.33 venous events and 6.10 arterial events per 10 000 woman-years). In a multivariable model, use of drospirenone carried an increased risk of venous thrombotic events, relative to both third-generation combined oral contraceptives (rate ratio [RR] 1.43, 95% confidence interval [CI] 1.15–1.78) and second-generation combined oral contraceptives (RR 1.65, 95% CI 1.02–2.65). There was no increase in the risk of arterial thrombosis with drospirenone.

Interpretation:

Use of drospirenone-containing oral contraceptives was associated with an increased risk of deep vein thrombosis and pulmonary embolism, but not transient ischemic attack or cerebrovascular attack, relative to second- and third-generation combined oral contraceptives.Oral hormonal therapy is the preferred method of contraception, especially among young women. In the United States in 2002, 12 million women were using “the pill.”¹ In a survey of households in Great Britain conducted in 2005 and 2006, one-quarter of women aged 16 to 49 years of age were using this form of contraception.² A large variety of combined oral contraceptive preparations are available, differing in terms of estrogen dose and in terms of the dose and type of the progestin component. Among preparations currently in use, the estrogen dose ranges from 15 to 35 μg, and the progestins are second-generation, third-generation or newer. The second-generation progestins (levonorgestrel and norgestrel), which are derivatives of testosterone, have differing degrees of androgenic and estrogenic activities. The structure of these agents was modified to reduce the androgenic activity, thus producing the third-generation progestins (desogestrel, gestodene and norgestimate). Newer progestins are chlormadinone acetate, a derivative of progesterone, and drospirenone, an analogue of the aldosterone antagonist spironolactone having antimineralo-corticoid and antiandrogenic activities. Drospirenone is promoted as causing less weight gain and edema than other forms of oral contraceptives, but few well-designed studies have compared the minor adverse effects of these drugs.³The use of oral contraceptives has been reported to confer an increased risk of venous and arterial thrombotic events,^4–7 specifically an absolute risk of venous thrombosis of 6.29 per 10 000 woman-years, compared with 3.01 per 10 000 woman-years among nonusers.⁸ It has long been accepted that there is a dose–response relationship between estrogen and the risk of venous thrombotic events. Reducing the estrogen dose from 50 μg to 20–30 μg has reduced the risk.⁹ Studies published since the mid-1990s have suggested a greater risk of venous thrombotic events with third-generation oral contraceptives than with second-generation formulations,^10–13 indicating that the risk is also progestin-dependent. The pathophysiological mechanism of the risk with different progestins is unknown. A twofold increase in the risk of arterial events (specifically ischemic stroke^6,14 and myocardial infarction⁷) has been observed in case–control studies for users of second-generation pills and possibly also third-generation preparations.^7,14Conflicting information is available regarding the risk of venous and arterial thrombotic events associated with drospirenone. An increased risk of venous thromboembolism, relative to second-generation pills, has been reported recently,^8,15,16 whereas two manufacturer-sponsored studies claimed no increase in risk.^17,18 In the study reported here, we investigated the risk of venous and arterial thrombotic events among users of various oral contraceptives in a large population-based cohort.     

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.     

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

Background

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

Methods

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

Results

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

Interpretation

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

San Francisco Syncope Rule to predict short-term serious outcomes: a systematic review

Background:

The San Francisco Syncope Rule has been proposed as a clinical decision rule for risk stratification of patients presenting to the emergency department with syncope. It has been validated across various populations and settings. We undertook a systematic review of its accuracy in predicting short-term serious outcomes.

Methods:

We identified studies by means of systematic searches in seven electronic databases from inception to January 2011. We extracted study data in duplicate and used a bivariate random-effects model to assess the predictive accuracy and test characteristics.

Results:

We included 12 studies with a total of 5316 patients, of whom 596 (11%) experienced a serious outcome. The prevalence of serious outcomes across the studies varied between 5% and 26%. The pooled estimate of sensitivity of the San Francisco Syncope Rule was 0.87 (95% confidence interval [CI] 0.79–0.93), and the pooled estimate of specificity was 0.52 (95% CI 0.43–0.62). There was substantial between-study heterogeneity (resulting in a 95% prediction interval for sensitivity of 0.55–0.98). The probability of a serious outcome given a negative score with the San Francisco Syncope Rule was 5% or lower, and the probability was 2% or lower when the rule was applied only to patients for whom no cause of syncope was identified after initial evaluation in the emergency department. The most common cause of false-negative classification for a serious outcome was cardiac arrhythmia.

Interpretation:

The San Francisco Syncope Rule should be applied only for patients in whom no cause of syncope is evident after initial evaluation in the emergency department. Consideration of all available electrocardiograms, as well as arrhythmia monitoring, should be included in application of the San Francisco Syncope Rule. Between-study heterogeneity was likely due to inconsistent classification of arrhythmia.Syncope is defined as sudden, transient loss of consciousness with the inability to maintain postural tone, followed by spontaneous recovery and return to pre-existing neurologic function.^1–5 It represents a common clinical problem, accounting for 1%–3% of visits to the emergency department and up to 6% of admissions to acute care hospitals.^6,7Assessment of syncope in patients presenting to the emergency department is challenging because of the heterogeneity of underlying pathophysiologic processes and diseases. Although many underlying causes of syncope are benign, others are associated with substantial morbidity or mortality, including cardiac arrhythmia, myocardial infarction, pulmonary embolism and occult hemorrhage.^4,8–10 Consequently, a considerable proportion of patients with benign causes of syncope are admitted for inpatient evaluation.^11,12 Therefore, risk stratification that allows for the safe discharge of patients at low risk of a serious outcome is important for efficient management of patients in emergency departments and for reduction of costs associated with unnecessary diagnostic workup.^12,13In recent years, various prediction rules based on the probability of an adverse outcome after an episode of syncope have been proposed.^3,14–16 However, the San Francisco Syncope Rule, derived by Quinn and colleagues in 2004,³ is the only prediction rule for serious outcomes that has been validated in a variety of populations and settings. This simple, five-step clinical decision rule is intended to identify patients at low risk of short-term serious outcomes^3,17 (Box 1).

Box 1:

San Francisco Syncope Rule³

AimPrediction of short-term (within 30 days) serious outcomes in patients presenting to the emergency department with syncope.DefinitionsSyncope: Transient loss of consciousness with return to baseline neurologic function. Trauma-associated and alcohol- or drug-related loss of consciousness excluded, as is definite seizure or altered mental status.Serious outcome: Death, myocardial infarction, arrhythmia, pulmonary embolism, stroke, subarachnoid hemorrhage, significant hemorrhage or any condition causing or likely to cause a return visit to the emergency department and admission to hospital for a related event.Selection of predictors in multivariable analysis: Fifty predictor variables were evaluated for significant associations with a serious outcome and combined to create a minimal set of predictors that are highly sensitive and specific for prediction of a serious outcome.Clinical decision ruleFive risk factors, indicated by the mnemonic “CHESS,” were identified to predict patients at high risk of a serious outcome:

• C – History of congestive heart failure
• H – Hematocrit < 30%
• E – Abnormal findings on 12-lead ECG or cardiac monitoring¹⁷ (new changes or nonsinus rhythm)
• S – History of shortness of breath
• S – Systolic blood pressure < 90 mm Hg at triage

Note: ECG = electrocardiogram.The aim of this study was to conduct a systematic review and meta-analysis of the accuracy of the San Francisco Syncope Rule in predicting short-term serious outcome for patients presenting to the emergency department with syncope.     

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.     

Risk of herpes zoster among patients with chronic obstructive pulmonary disease: a population-based study

Background

Systemic inflammation and dysregulated immune function in chronic obstructive pulmonary disease (COPD) is hypothesized to predispose patients to development of herpes zoster. However, the risk of herpes zoster among patients with COPD is undocumented. We therefore aimed to investigate the risk of herpes zoster among patients with COPD.

Methods

We conducted a cohort study using data from the Taiwan Longitudinal Health Insurance Database. We performed Cox regressions to compare the hazard ratio (HR) of herpes zoster in the COPD cohort and in an age- and sex-matched comparison cohort. We divided the patients with COPD into three groups according to use of steroid medications and performed a further analysis to examine the risk of herpes zoster.

Results

The study included 8486 patients with COPD and 33 944 matched control patients. After adjustment for potential confounding factors, patients with COPD were more likely to have incidents of herpes zoster (adjusted HR 1.68, 95% confidence interval [CI] 1.45–1.95). When compared with the comparison cohort, the adjusted HR of herpes zoster was 1.67 (95% CI 1.43–1.96) for patients with COPD not taking steroid medications. The adjusted HR of herpes zoster was slightly greater for patients with COPD using inhaled corticosteroids only (adjusted HR 2.09, 95% CI 1.38–3.16) and was greatest for patients with COPD using oral steroids (adjusted HR 3.00, 95% CI 2.40–3.75).

Interpretation

Patients with COPD were at increased risk of herpes zoster relative to the general population. The relative risk of herpes zoster was greatest for patients with COPD using oral steroids.Herpes zoster is caused by a reactivation of latent varicella-zoster virus residing in sensory ganglia after an earlier episode of varicella.¹ Herpes zoster is characterized by a painful vesicular dermatomal rash. It is commonly complicated with chronic pain (postherpetic neuralgia), resulting in reduced quality of life and functional disability to a degree comparable to that experienced by patients with congestive heart failure, diabetes mellitus and major depression.^1,2 Patients with herpes zoster experience more substantial role limitations resulting from emotional and physical problems than do patients with congestive heart failure or diabetes.³ Pain scores for postherpetic neuralgia have been shown to be as high as those for chronic pain from osteoarthritis and rheumatoid arthritis.³ Although aging is the most well-known risk factor for herpes zoster, people with diseases associated with impaired immunity, such as malignancy, HIV infection, diabetes and rheumatic diseases, are also at higher risk for herpes zoster.^4,5Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow limitation that is associated with an abnormal inflammatory response by the small airways and alveoli to inhaled particles and pollutants.⁶ Disruption of local defence systems (e.g., damage to the innate immune system, impaired mucociliary clearance) predispose patients with COPD to respiratory tract infections. Each infection can cause exacerbation of COPD and further deterioration of lung function, which in turn increase predisposition to infection.^7,8There is increasing evidence that COPD is an autoimmune disease, with chronic systemic inflammation involving more than just the airways and lungs.⁶ Given that various immune-mediated diseases (e.g., rheumatoid arthritis, inflammatory bowel disease) have been reported to be associated with an increased risk of herpes zoster,^4,9,10 it is reasonable to hypothesize that the immune dysregulation found in COPD may put patients at higher risk of developing herpes zoster. In addition, inhaled or systemic corticosteroids used for management of COPD can increase susceptibility to herpes zoster by suppressing normal immune function.¹¹ However, data are limited regarding the risk of herpes zoster among patients with COPD.The goal of our study was to investigate whether patients with COPD have a higher incidence of herpes zoster than the general population. In addition, we aimed to examine the risk for herpes zoster with and without steroid therapy among patients with COPD relative to the general 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.     

The potential economic impact of restricted access to angiotensin-receptor blockers

Background

The use of angiotensin-receptor blockers increased by more than 4000% in Canada from 1996 to 2006. The benefit of these medications over angiotensin-converting-enzyme (ACE) inhibitors has not been proven aside from a reduction in dry cough. We estimated the potential cost savings that might have been achieved had access to angiotensin-receptor blockers been restricted.

Methods

We performed a cost-minimization analysis with a decision-tree model using a societal perspective over a one-year period. Sources of data for model parameters included IMS Health Canada data collected from one-third of all retail pharmacies for the cost and use of angiotensin-receptor blockers and ACE inhibitors in each province, as well as published studies for administrative costs and incidence of dry cough. We used Monte Carlo simulations with 10 000 iterations to test the impact of several model parameters (e.g., drug prices, administrative costs and the incidence of dry cough). All data are in 2006 Canadian dollars.

Results

A policy that would have restricted access to angiotensin-receptor blockers might have saved more than $77 million in Canada in 2006. The simulations yielded similar savings for the year (mean $58.3 million, 95% confidence interval $29.3 million to $90.8 million). Every simulation showed a cost savings.

Interpretation

Had access to angiotensin-receptor blockers been restricted, the potential cost savings to the Canadian health care system might have been more than $77 million in 2006, likely without any adverse effect on cardiovascular health.Costs of cardiovascular drugs in Canada increased by more than 200% from 1996 to 2006. The use of angiotensin-receptor blockers grew at an especially high rate, rising by more than 4000% during that period.¹ Such an increase in the use of these agents is not strongly supported by evidence.¹ Although angiotensin-receptor blockers were effective in reducing mortality and morbidity associated with hypertension in one large trial, patients in the control group were not given an angiotensin-converting-enzyme (ACE) inhibitor.² Instead, they received atenolol, a β-blocker, a drug class whose use is increasingly being questioned in the management of high blood pressure uncomplicated by prior myocardial infarction, heart failure or tachyarrhythmia.^3,4 Although angiotensin-receptor blockers are not associated with dry cough, a side effect reported by 5%–35% of patients taking ACE inhibitors,⁵ this side effect is benign and fully reversible once the drug is stopped. Meta-analyses that included several randomized trials failed to show superiority of angiotensin-receptor blockers over ACE inhibitors for the treatment of hypertension,⁶ heart failure⁷ or the secondary prevention of coronary artery disease.⁸Innovative policies are needed to offset the ever-increasing costs of cardiovascular drugs in Canada. Currently, British Columbia is the only province that restricts access to angiotensin-receptor blockers. Given that these agents can safely be substituted by ACE inhibitors and still yield similar clinical outcomes,^6–8 restricting their access is expected to lead to cost savings without adversely affecting patient heath. We estimated the potential cost savings that might have been achieved had access to angiotensin-receptor blockers been restricted in Canada in 2006.     

Association of practice size and pay-for-performance incentives with the quality of diabetes management in primary care

Background:

Not enough is known about the association between practice size and clinical outcomes in primary care. We examined this association between 1997 and 2005, in addition to the impact of the Quality and Outcomes Framework, a pay-for-performance incentive scheme introduced in the United Kingdom in 2004, on diabetes management.

Methods:

We conducted a retrospective open-cohort study using data from the General Practice Research Database. We enrolled 422 general practices providing care for 154 945 patients with diabetes. Our primary outcome measures were the achievement of national treatment targets for blood pressure, glycated hemoglobin (HbA_1c) levels and total cholesterol.

Results:

We saw improvements in the recording of process of care measures, prescribing and achieving intermediate outcomes in all practice sizes during the study period. We saw improvement in reaching national targets after the introduction of the Quality and Outcomes Framework. These improvements significantly exceeded the underlying trends in all practice sizes for achieving targets for cholesterol level and blood pressure, but not for HbA_1c level. In 1997 and 2005, there were no significant differences between the smallest and largest practices in achieving targets for blood pressure (1997 odds ratio [OR] 0.98, 95% confidence interval [CI] 0.82 to 1.16; 2005 OR 0.92, 95% CI 0.80 to 1.06 in 2005), cholesterol level (1997 OR 0.94, 95% CI 0.76 to 1.16; 2005 OR 1.1, 95% CI 0.97 to 1.40) and glycated hemoglobin level (1997 OR 0.79, 95% CI 0.55 to 1.14; 2005 OR 1.05, 95% CI 0.93 to 1.19).

Interpretation:

We found no evidence that size of practice is associated with the quality of diabetes management in primary care. Pay-for-performance programs appear to benefit both large and small practices to a similar extent.There is a well-established body of literature showing positive associations between volume of patients and clinical outcomes in health care, which has been documented by a systematic review.¹ However, this association has usually been examined in a limited number of discrete procedures, and most studies have involved hospital-based services rather than primary care settings.^2–5Improving our understanding of the association between volume of patients and outcomes in primary care is important for several reasons. First, most contacts with health systems occur in primary care settings, and optimizing the delivery of these services has the potential to improve the health of the population.⁶ Second, over the past decade, primary care has assumed greater responsibility for managing the growing burden of chronic disease.^7,8 Larger providers may be better resourced, through the employment of additional support staff and greater use of information technology, to deliver the systematic, structured care necessary for the effective management of chronic disease.^6,9 Third, larger providers may have been more responsive to nonfinancial and financial incentives, including pay for performance, implemented by payers aimed at improving the quality of care.^7,10 Fourth, in many countries, primary care is based around a predominance of small practices.^6,11,12 In 2006, 53% of practices in England and Wales had three or fewer family physicians.¹¹ In the same year in the United States, 30.3% of family physicians were in solo practice; 9.4% were in two-physician practices.¹²Despite the limited data available, concerns have been raised about the standards of care delivered by smaller family practices.¹³ In the United Kingdom and Canada, this has resulted in an explicit policy objective of encouraging smaller practices to amalgamate.^13,14Our study examines the associations between the size of practice and the quality of diabetes management in UK primary care settings between 1997 and 2005. We tested the hypotheses that patients attending larger family practices receive better care for diabetes and that the quality gap between larger and smaller practices has increased over the past decade. We also hypothesized that larger practices derived more benefit from the Quality and Outcomes Framework, a major pay-for-performance program in primary care introduced in 2004.     

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 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.     

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.     

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

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

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

Background:

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

Methods:

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

Results:

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

Interpretation:

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

Cost-effectiveness of the use of low- and high-potency statins in people at low cardiovascular risk

Background:

Although statins have been shown to reduce the risk of cardiovascular events in patients at low cardiovascular risk, their absolute benefit is small in the short term, which may adversely affect cost-effectiveness. We sought to determine the long-term cost-effectiveness (beyond the duration of clinical trials) of low- and high-potency statins in patients at low cardiovascular risk and to estimate the impact on Canada’s publicly funded health care system.

Methods:

Using Markov modelling, we performed a cost-utility analysis in which we compared low-potency statins (fluvastatin, lovastatin, pravastatin and simvastatin) and high-potency statins (atorvastatin and rosuvastatin) with no statins in a simulated cohort of low-risk patients over a lifetime horizon. Model outcomes included costs (in 2010 Canadian dollars), quality-adjusted life-years (QALYs) gained and the cost per QALY gained.

Results:

Over a lifetime horizon, the cost of managing a patient at low cardiovascular risk was estimated to be about $10 100 without statins, $15 200 with low-potency statins and $16 400 with high-potency statins. The cost per QALY gained with high-potency statins (v. no statins) was $21 300; the use of low-potency statins was not considered economically attractive. These results were robust to sensitivity analyses, although their use became economically unattractive when the duration of benefit from statin use was assumed to be less than 10 years.

Interpretation:

Use of high-potency statins in patients at low cardiovascular risk was associated with a cost per QALY gained that was economically attractive by current standards, assuming that the benefit from statin use would continue for at least 10 years. However, the overall expenditure on statins would be substantial, and the ramifications of this practice should be carefully considered by policy-makers.Although statins improve survival and reduce the risk of cardiovascular events in populations at high and moderate risk,¹ their effectiveness and cost-effectiveness in low-risk populations is less certain.² This uncertainly is due in part to low-risk patients being less likely to have cardiovascular events over the short term. For instance, in the recent Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) study³ — a large randomized trial comparing cardiovascular outcomes in low-risk patients randomly assigned to receive either rosuvastatin or placebo — the risk of death or nonfatal myocardial infarction over three years was 2.5% in the rosuvastatin group and 3.5% in the placebo group, which represented a large relative, but small absolute, risk reduction in cardiovascular events.Other cholesterol-lowering interventions are available, such as diet, exercise and the use of other hypolipidemic agents, but the use of statins is the only such intervention known to reduce cardiovascular risk in people with low and high blood cholesterol levels.^4–7 Thus, statins are now primarily indicated for the reduction of cardiovascular risk instead of being used mainly for the management of hypercholesterolemia.⁸With this broadening indication for use, expenditures on statins have increased and represent about 13% of total expenditures by provincial formularies in Canada.⁹ The absolute number of people at low cardiovascular risk who are taking statins has increased substantially over the last decade, driven by the large number of low-risk people in the general population.¹⁰ In addition, statins that are more effective in lowering low-density lipoprotein (LDL) cholesterol levels have become available.^3,11 These high-potency statins (atorvastatin and rosuvastatin) are substantially more expensive than low-potency statins available as generics (pravastatin, simvastatin, fluvastatin and lovastatin), although atorvastatin has recently become available as a generic in Canada.¹² Increasing costs and concerns over the absolute benefit of statins in people at low cardiovascular risk has raised concerns about the cost-effectiveness of statins in this group.We performed an incremental cost-utility analysis comparing low- and high-potency statins with no statins in patients at low cardiovascular risk in a Canadian setting. We used findings from our group’s recent systematic review of the efficacy of statins for primary prevention in low-risk people¹³ as well as observational data from a large provincial registry of patients documenting existing statin use. Our objective was to determine which strategy represents the best use of health care resources for the publicly funded health care system, and what investment would be required to fund statins.