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besity is a complex chronic disease in which abnormal or excess body fat (adiposity) impairs health, increases the risk of long-term medical complications and reduces lifespan. 1 Epidemiologic studies define obesity using the body mass index (BMI; weight/height 2 ), which can stratify obesity-related health risks at the population level. Obesity is operationally defined as a BMI exceeding 30 kg/m 2 and is subclassified into class 1 (30-34.9), class 2 (35-39.9) and class 3 ( 40). At the population level, health complications from excess body fat increase as BMI increases. At the individual level, complications occur because of excess adiposity, location and distribution of adiposity and many other factors, including environmental, genetic, biologic and socioeconomic factors (Box 1). ver the past 3 decades, the prevalence of obesity has steadily increased throughout the world, Importantly, severe obesity has increased more than fourfold and, in 2016, affected an estimated 1.9 million Canadian adults. besity has become a major public health issue that increases health care costs People with obesity experience pervasive weight bias and stigma, which contributes (independent of weight or BMI) to increased morbidity and mortality. 17 Obesity is caused by the complex interplay of multiple genetic, metabolic, behavioural and environmental factors, with the latter thought to be the proximate cause of the substantial GUIDELINE

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The ability to work with professionals from other disciplines to deliver collaborative, patient-centred care is considered a critical element of professional practice requiring a specific set of competencies. However, a generally accepted framework for collaborative competencies is missing, which makes consistent preparation of students and staff challenging. Some authors have argued that there is a lack of conceptual clarity of the "active ingredients" of collaboration relating to quality of care and patient outcomes, which may be at the root of the competencies issue. As part of a large Health Canada funded study focused on interprofessional education and collaborative practice, our goal was to understand the competencies for collaborative practice that are considered most relevant by health professionals working at the front line. Interview participants comprised 60 health care providers from various disciplines. Understanding and appreciating professional roles and responsibilities and communicating effectively emerged as the two perceived core competencies for patient-centred collaborative practice. For both competencies there is evidence of a link to positive patient and provider outcomes. We suggest that these two competencies should be the primary focus of student and staff education aimed at increasing collaborative practice skills.

BACKGROUND: The results from controlled clinical trials investigating the efficacy of azathioprine and 6-mercaptopurine for the treatment of active Crohn's disease have been conflicting and controversial. An updated meta-analysis was performed to assess the effectiveness of these drugs for the induction of remission in active Crohn's disease. OBJECTIVES: The primary objective was to determine the efficacy and safety of azathioprine and 6-mercaptopurine for induction of remission in active Crohn's disease. SEARCH METHODS: We searched MEDLINE, EMBASE and the Cochrane Library from inception to 30 October 2015. Review articles and conference proceedings were also searched to identify additional studies. SELECTION CRITERIA: Randomized controlled trials (RCTs) of oral azathioprine or 6-mercaptopurine compared to placebo or active therapy involving adult patients with active Crohn's disease were selected for inclusion. DATA COLLECTION AND ANALYSIS: Data were extracted by two independent observers based on the intention-to-treat principle. Outcomes of interest included: clinical remission, clinical improvement, fistula improvement or healing, steroid sparing, adverse events, withdrawals due to adverse events and serious adverse events. We calculated the pooled relative risk (RR) and 95% confidence intervals (95% CI) for each outcome. The methodological quality of included studies was evaluated using the Cochrane risk of bias tool. The overall quality of the evidence supporting each outcome was assessed using the GRADE criteria. MAIN RESULTS: Thirteen RCTs (n = 1211 patients) of azathioprine and 6-mercaptopurine therapy in adult patients were identified: nine included placebo comparators and six included active comparators. The majority of included studies were rated as low risk of bias. There was no statistically significant difference in clinical remission rates between azathioprine or 6-mercaptopurine and placebo. Forty-eight per cent (95/197) of patients receiving antimetabolites achieved remission compared to 37% (68/183) of placebo patients (5 studies, 380 patients; RR 1.23, 95% CI 0.97 to 1.55). There was no statistically significant difference in clinical improvement rates between azathioprine or 6-mercaptopurine and placebo. Forty-eight per cent (107/225) of patients receiving antimetabolites achieved clinical improvement or remission compared to 36% (75/209) of placebo patients (8 studies, 434 patients; RR 1.26, 95% CI 0.98 to 1.62). There was a statistically significant difference in steroid sparing (defined as prednisone dose < 10 mg/day while maintaining remission) between azathioprine and placebo. Sixty-four per cent (47/163) of azathioprine patients were able to reduce their prednisone dose to < 10 mg/day compared to 46% (32/70) of placebo patients (RR 1.34, 95% CI 1.02 to 1.77). GRADE analyses rated the overall quality of the evidence for the outcomes clinical remission, clinical improvement and steroid sparing as moderate due to sparse data. There was no statistically significant difference in withdrawals due to adverse events or serious adverse events between antimetabolites and placebo. Ten percent of patients in the antimetabolite group withdrew due to adverse events compared to 5% of placebo patients (8 studies, 510 patients; RR 1.70, 95% CI 0.94 to 3.08). Serious adverse events were reported in 14% of patients receiving azathioprine compared to 4% of placebo patients (2 studies, 216 patients; RR 2.57, 95% CI 0.92 to 7.13). Common adverse events reported in the placebo controlled studies included: allergic reactions. leukopenia, pancreatitis and nausea. Azathioprine was significantly inferior to infliximab for induction of steroid-free clinical remission. Thirty per cent (51/170) of azathioprine patients achieved steroid-free remission compared to 44% (75/169) of infliximab patients (1 study, 339 patients; RR 0.68, 95% CI 0.51 to 0.90). The combination of azathioprine and infliximab was significantly superior to infliximab alone for induction of steroid-free clinical remission. Sixty per cent (116/194) of patients in the combined azathioprine and infliximab group achieved steroid-free remission compared to 48% (91/189) of infliximab patients (2 studies, 383 patients; RR 1.23, 95% CI 1.02 to 1.47). Azathioprine or 6-mercaptopurine therapy was found to be no better at inducing steroid free clinical remission compared to methotrexate (RR 1.13, 95% CI 0.85 to 1.49) and 5-aminosalicylate or sulfasalazine (RR 1.24, 95% CI 0.80 to 1.91). There were no statistically significant differences in withdrawals due to adverse events between azathioprine or 6-mercaptopurine and methotrexate (RR 0.78, 95% CI 0.23 to 2.71); between azathioprine or 6-mercaptopurine and 5-aminosalicylate or sulfasalazine (RR 0.98, 95% CI 0.38 to 2.54); between azathioprine and infliximab (RR 1.47, 95% CI 0.96 to 2.23); or between the combination of azathioprine and infliximab and infliximab (RR 1.16, 95% CI 0.75 to 1.80). Common adverse events in the active comparator trials included nausea, abdominal pain, pyrexia and headache. AUTHORS' CONCLUSIONS: Azathioprine and 6-mercaptopurine offer no advantage over placebo for induction of remission or clinical improvement in active Crohn's disease. Antimetaboilte therapy may allow patients to reduce steroid consumption. Adverse events were more common in patients receiving antimetabolites although differences with placebo were not statistically significant. Azathioprine therapy is inferior to infliximab for induction of steroid-free remission. However, the combination of azathioprine and infliximab was superior to infliximab alone for induction of steroid-free remission.

BACKGROUND: Comorbidity risk adjustment methods have been used widely with administrative data, and the Charlson/Deyo method is perhaps the most commonly used in the literature. However, a new method defined by Elixhauser et al. has been introduced recently and could be superior, although it has not been validated widely. OBJECTIVES: We compared the Charlson/Deyo and Elixhauser methods using Canadian administrative data on patients with myocardial infarction (MI). RESEARCH DESIGN: We conducted a historical cohort study. SUBJECTS: We used administrative hospital discharge data from a large Canadian city for all cases with acute MI coded as most responsible diagnosis between January 1, 1995, and March 31, 2001. MEASURES: We used each of the 2 methods to define comorbidity variables based on the International Classification of Diseases, 9th Revision, Clinical Modification codes present in each case record. We then compared 2 models predicting in-hospital mortality based on presence or absence of the variables defined by each of the methods. Frequency tables were produced and c-statistics and changes in -2 log likelihood (-2LogL) were calculated. We also visually assessed model performance by plotting observed and expected percentages of death for increasing risk categories defined by the 2 models. RESULTS: The Elixhauser model outperformed the Charlson/Deyo model in predicting mortality, with higher c-statistic values (0.793 vs. 0.704). Superior performance of the Elixhauser method is confirmed when plotting the expected and observed risks of death across groupings of increasing risk, in which the Elixhauser method yields a wider range of predicted and observed probabilities of death across groupings (2.5%-33%) than does the Charlson/Deyo method (5%-25%). CONCLUSIONS: The Elixhauser comorbidity measurement method performs better than the widely used Charlson/Deyo method in the Canadian acute MI cases studied.

An individual participant data meta-analysis was conducted in the data of 14 673 Japanese participants without a history of cardiovascular disease (CVD) to examine the association of the brachial-ankle pulse wave velocity (baPWV) with the risk of development of CVD. During the average 6.4-year follow-up period, 687 participants died and 735 developed cardiovascular events. A higher baPWV was significantly associated with a higher risk of CVD, even after adjustments for conventional risk factors ( P for trend &lt;0.001). When the baPWV values were classified into quintiles, the multivariable-adjusted hazard ratio for CVD increased significantly as the baPWV quintile increased. The hazard ratio in the subjects with baPWV values in quintile 5 versus that in those with the values in quintile 1 was 3.50 (2.14–5.74; P &lt;0.001). Every 1 SD increase of the baPWV was associated with a 1.19-fold (1.10–1.29; P &lt;0.001) increase in the risk of CVD. Moreover, addition of baPWV to a model incorporating the Framingham risk score significantly increased the C statistics from 0.8026 to 0.8131 ( P &lt;0.001) and also improved the category-free net reclassification (0.247; P &lt;0.001). The present meta-analysis clearly established baPWV as an independent predictor of the risk of development of CVD in Japanese subjects without preexisting CVD. Thus, measurement of the baPWV could enhance the efficacy of prediction of the risk of development of CVD over that of the Framingham risk score, which is based on the traditional cardiovascular risk factors.

INTRODUCTION: We undertook a meta-analysis of the Continuing Medical Education (CME) outcome literature to examine the effect of moderator variables on physician knowledge, performance, and patient outcomes. METHODS: A literature search of MEDLINE and ERIC was conducted for randomized controlled trials and experimental design studies of CME outcomes in which physicians were a major group. CME moderator variables included the types of intervention, the types and number of participants, time, and the number of intervention sessions held over time. RESULTS: Thirty-one studies met the eligibility criteria, generating 61 interventions. The overall sample-size weighted effect size for all 61 interventions was r = 0.28 (0.18). The analysis of CME moderator variables showed that active and mixed methods had medium effect sizes (r = 0.33 [0.33], r = 0.33 [0.26], respectively), and passive methods had a small effect size (r = 0.20 [0.16], confidence interval 0.15, 0.26). There was a positive correlation between the effect size and the length of the interventions (r = 0.33) and between multiple interventions over time (r = 0.36). There was a negative correlation between the effect size and programs that involved multiple disciplines (r = -0.18) and the number of participants (r = -0.13). The correlation between the effect size and the length of time for outcome assessment was negative (r = -0.31). DISCUSSION: The meta-analysis suggests that the effect size of CME on physician knowledge is a medium one; however, the effect size is small for physician performance and patient outcome. The examination of moderator variables shows there is a larger effect size when the interventions are interactive, use multiple methods, and are designed for a small group of physicians from a single discipline.

BACKGROUND: Whether consumption of sugar-sweetened beverages (SSBs) or artificially sweetened beverages (ASBs) is associated with risk of mortality is of public health interest. METHODS: We examined associations between consumption of SSBs and ASBs with risk of total and cause-specific mortality among 37 716 men from the Health Professional's Follow-up study (from 1986 to 2014) and 80 647 women from the Nurses' Health study (from 1980 to 2014) who were free from chronic diseases at baseline. Cox proportional hazards regression was used to estimate hazard ratios and 95% confidence intervals. RESULTS: We documented 36 436 deaths (7896 cardiovascular disease [CVD] and 12 380 cancer deaths) during 3 415 564 person-years of follow-up. After adjusting for major diet and lifestyle factors, consumption of SSBs was associated with a higher risk of total mortality; pooled hazard ratios (95% confidence intervals) across categories (<1/mo, 1-4/mo, 2-6/week, 1-<2/d, and ≥2/d) were 1.00 (reference), 1.01 (0.98, 1.04), 1.06 (1.03, 1.09), 1.14 (1.09, 1.19), and 1.21 (1.13, 1.28; P trend <0.0001). The association was observed for CVD mortality (hazard ratio comparing extreme categories was 1.31 [95% confidence interval, 1.15, 1.50], P trend <0.0001) and cancer mortality (1.16 [1.04, 1.29], P trend =0.0004). ASBs were associated with total and CVD mortality in the highest intake category only; pooled hazard ratios (95% confidence interval) across categories were 1.00 (reference), 0.96 (0.93, 0.99), 0.97 (0.95, 1.00), 0.98 (0.94, 1.03), and 1.04 (1.02, 1.12; P trend = 0.01) for total mortality and 1.00 (reference), 0.93 (0.87, 1.00), 0.95 (0.89, 1.00), 1.02 (0.94, 1.12), and 1.13 (1.02, 1.25; P trend = 0.02) for CVD mortality. In cohort-specific analysis, ASBs were associated with mortality in NHS (Nurses' Health Study) but not in HPFS (Health Professionals Follow-up Study) ( P interaction, 0.01). ASBs were not associated with cancer mortality in either cohort. CONCLUSIONS: Consumption of SSBs was positively associated with mortality primarily through CVD mortality and showed a graded association with dose. The positive association between high intake levels of ASBs and total and CVD mortality observed among women requires further confirmation.

INTRODUCTION: Integrated health systems are considered a solution to the challenge of maintaining the accessibility and integrity of healthcare in numerous jurisdictions worldwide. However, decision makers in a Canadian health region indicated they were challenged to find evidence-based information to assist with the planning and implementation of integrated healthcare systems. METHODS: A systematic literature review of peer-reviewed literature from health sciences and business databases, and targeted grey literature sources. RESULTS: Despite the large number of articles discussing integration, significant gaps in the research literature exist. There was a lack of high quality, empirical studies providing evidence on how health systems can improve service delivery and population health. No universal definition or concept of integration was found and multiple integration models from both the healthcare and business literature were proposed in the literature. The review also revealed a lack of standardized, validated tools that have been systematically used to evaluate integration outcomes. This makes measuring and comparing the impact of integration on system, provider and patient level challenging. DISCUSSION AND CONCLUSION: Healthcare is likely too complex for a one-size-fits-all integration solution. It is important for decision makers and planners to choose a set of complementary models, structures and processes to create an integrated health system that fits the needs of the population across the continuum of care. However, in order to have evidence available, decision makers and planners should include evaluation for accountability purposes and to ensure a better understanding of the effectiveness and impact of health systems integration.

OBJECTIVE: To provide a comprehensive review of the literature on the measurement, correlates, and health outcomes of medication adherence among community-dwelling older adults. DATA SOURCES: Searches of MEDLINE, PubMed, and International Pharmaceutical Abstracts databases for English-language literature (1966-December 2002) were conducted using one or more of the following terms: elderly, adherence/nonadherence, compliance/noncompliance, medication/drug, methodology/measurement, and hospitalization. STUDY SELECTION AND DATA EXTRACTION: From the above search, studies of medication adherence in community-dwelling seniors were selected for review along with relevant publications from the reference lists of articles identified in the initial database search. DATA SYNTHESIS: Although several methods are available for the assessment of adherence, accurate measurement continues to be difficult. The available evidence suggests that polypharmacy and poor patient-healthcare provider relationships (including the use of multiple providers) may be major determinants of nonadherence among older persons, with the impact of most sociodemographic factors being negligible. There is little consensus regarding other determinants of nonadherence. Relatively few high-quality investigations have examined the associations between nonadherence and subsequent health outcomes. Available data provide some support for increased health risks with nonadherence. However, interventions to improve adherence have seldom demonstrated positive effects on health outcomes. CONCLUSIONS: There are few empirical data to support a simple systematic descriptor of the nonadherent patient. The inconsistencies across studies may be attributable, in part, to the inherent difficulties involved in the measurement of a behavioral risk factor such as nonadherence. Future research in this area would be strengthened by incorporation of detailed assessments of patient-reported reasons for nonadherence, the appropriateness of drug regimens, and the effect of nonadherence on health outcomes.

BACKGROUND: The risk of stroke is elevated in the first 48 hours after TIA. Previous prognostic models suggest that diabetes mellitus, age, and clinical symptomatology predict stroke. The authors evaluated the magnitude of risk of stroke and predictors of stroke after TIA in an entire population over time. METHODS: Administrative data from four different databases were used to define TIA and stroke for the entire province of Alberta for the fiscal year (April 1999-March 2000). The age-adjusted incidence of TIA was estimated using direct standardization to the 1996 Canadian population. The risk of stroke after a diagnosis of TIA in an Alberta emergency room was defined using a Kaplan-Meier survival function. Cox proportional hazards modeling was used to develop adjusted risk estimates. Risk assessment began 24 hours after presentation and therefore the risk of stroke in the first few hours after TIA is not captured by our approach. RESULTS: TIA was reported among 2,285 patients for an emergency room diagnosed, age-adjusted incidence of 68.2 per 100,000 population (95% CI 65.3 to 70.9). The risk of stroke after TIA was 9.5% (95% CI 8.3 to 10.7) at 90 days and 14.5% (95% CI 12.8 to 16.2) at 1 year. The risk of combined stroke, myocardial infarction, or death was 21.8% (95% CI 20.0 to 23.6) at 1 year. Hypertension, diabetes mellitus, and older age predicted stroke at 1 year but not earlier. CONCLUSIONS: Although stroke is common after TIA, the early risk is not predicted by clinical and demographic factors. Validated models to identify which patients require urgent intervention are needed.

BACKGROUND: Chronic low back pain is, in many countries, the main cause of long term disability in middle age. Patients with chronic low back pain are often referred for multidisciplinary treatment. Previous published systematic reviews on this topic included no randomised controlled trials and pooled together controlled and non-controlled studies. OBJECTIVES: To assess the effect of multidisciplinary bio-psycho-social rehabilitation on pain, function, employment, quality of life and global assessment outcomes in subjects with chronic disabling low back pain. SEARCH STRATEGY: We searched MEDLINE, EMBASE, PsychLIT, CINAHL, Health STAR, and The Cochrane Library from the beginning of the database to June 1998 using the comprehensive search strategy recommended by the Back Review Group of the Cochrane Collaboration. INTERVENTION specific key words for this review were: patient care team, patient care management, multidisciplinary, interdisciplinary, multiprofessional, multimodal, pain clinic and functional restoration. We also reviewed reference lists and consulted the editors of the Back Review Group of the Cochrane Collaboration. DESIGN: randomised controlled trials comparing multidisciplinary bio-psycho-social rehabilitation with a non-multidisciplinary control intervention. POPULATION: Adults with disabling low back pain of more than three months in duration. INTERVENTION: Patients had to be assessed and treated by qualified professionals according to a plan that addresses physical and at least one of psychological, or social/occupational dimensions. OUTCOMES: Only trials which reported treatment effect in at least one of pain, function, employment status, quality of life or global improvement. Exclusion: Pure educational interventions (back schools) and pure physical interventions were excluded. DATA COLLECTION AND ANALYSIS: Selection, data extraction and quality grading of studies was done by two independent reviewers using pre-tested data forms. Study quality was assessed according to the scheme recommended by the Back Review Group of the Cochrane Collaboration. Trials with internal validity scores of five or more in a ten point scale were considered high quality. Discrepancies between reviewers were resolved by consensus or by a third reviewer. Given the marked heterogeneity in study settings, interventions and control groups we decided not to pool trial results in a meta-analysis. Instead, we summarized findings by strength of evidence and nature of intervention and control treatments. The evidence was judged to be strong when multiple high quality trials produced generally consistent findings. It was judged to be moderate when multiple low quality or one high quality and one or more low quality trials produced generally consistent findings. Evidence was considered to be limited when only one randomised trial existed or if findings of existing trials were inconsistent. MAIN RESULTS: Ten trials (12 randomised comparisons) were included. They randomised a total of 1964 patients with chronic low back pain. There was strong evidence that intensive multidisciplinary bio-psycho-social rehabilitation with a functional restoration approach improved function when compared with inpatient or outpatient non-multidisciplinary treatments. There was moderate evidence that intensive multidisciplinary bio-psycho-social rehabilitation with a functional restoration approach improved pain when compared with outpatient non-multidisciplinary rehabilitation or usual care. There was contradictory evidence regarding vocational outcomes of intensive multidisciplinary bio-psycho-social intervention. Some trials reported improvements in work readiness, but others showed no significant reduction in sickness leaves. Less intensive outpatient psycho-physical treatments did not improve pain, function or vocational outcomes when compared with non-multidisciplinary outpatient therapy or usual care. Few trials reported effects on quality of life or global assessments. REVIEWER'S CONCLUSIONS: The reviewed trials provide evidence that intensive multidisciplinary bio-psycho-social rehabilitation with a functional restoration approach improves pain and function. Less intensive interventions did not show improvements in clinically relevant outcomes.

BACKGROUND: The performance of the Charlson and Elixhauser comorbidity measures in predicting patient outcomes have been well validated with ICD-9 data but not with ICD-10 data, especially in disease specific patient cohorts. The objective of this study was to assess the performance of these two comorbidity measures in the prediction of in-hospital and 1 year mortality among patients with congestive heart failure (CHF), diabetes, chronic renal failure (CRF), stroke and patients undergoing coronary artery bypass grafting (CABG). METHODS: A Canadian provincial hospital discharge administrative database was used to define 17 Charlson comorbidities and 30 Elixhauser comorbidities. C-statistic values were calculated to evaluate the performance of two measures. One year mortality information was obtained from the provincial Vital Statistics Department. RESULTS: The absolute difference between ICD-9 and ICD-10 data in C-statistics ranged from 0 to 0.04 across five cohorts for the Charlson and Elixhauser comorbidity measures predicting in-hospital or 1 year mortality. In the models predicting in-hospital mortality using ICD-10 data, the C-statistics ranged from 0.62 (for stroke) - 0.82 (for diabetes) for Charlson measure and 0.62 (for stroke) to 0.83 (for CABG) for Elixhauser measure. CONCLUSION: The change in coding algorithms did not influence the performance of either the Charlson or Elixhauser comorbidity measures in the prediction of outcome. Both comorbidity measures were still valid prognostic indicators in the ICD-10 data and had a similar performance in predicting short and long term mortality in the ICD-9 and ICD-10 data.

The proportion of overweight and obese adults in the United States and Canada has increased over the past decade, but temporal trends in body mass index (BMI) and weight gain on antiretroviral therapy (ART) among HIV-infected adults have not been well characterized. We conducted a cohort study comparing HIV-infected adults in the North America AIDS Cohort Collaboration on Research and Design (NA-ACCORD) to United States National Health and Nutrition Examination Survey (NHANES) controls matched by sex, race, and age over the period 1998 to 2010. Multivariable linear regression assessed the relationship between BMI and year of ART initiation, adjusting for sex, race, age, and baseline CD4(+) count. Temporal trends in weight on ART were assessed using a generalized least-squares model further adjusted for HIV-1 RNA and first ART regimen class. A total of 14,084 patients from 17 cohorts contributed data; 83% were male, 57% were nonwhite, and the median age was 40 years. Median BMI at ART initiation increased from 23.8 to 24.8 kg/m(2) between 1998 and 2010 in NA-ACCORD, but the percentage of those obese (BMI ≥30 kg/m(2)) at ART initiation increased from 9% to 18%. After 3 years of ART, 22% of individuals with a normal BMI (18.5-24.9 kg/m(2)) at baseline had become overweight (BMI 25.0-29.9 kg/m(2)), and 18% of those overweight at baseline had become obese. HIV-infected white women had a higher BMI after 3 years of ART as compared to age-matched white women in NHANES (p = 0.02), while no difference in BMI after 3 years of ART was observed for HIV-infected men or non-white women compared to controls. The high prevalence of obesity we observed among ART-exposed HIV-infected adults in North America may contribute to health complications in the future.

An improved method for allele replacement in Pseudomonas aeruginosa was developed. The two main ingredients of the method are: (i) novel ColE1-type cloning vectors derived from pBR322 and pUC19; and (ii) a family of cassettes containing a portable oriT, the sacB gene from Bacillus subtilis as a counter-selectable marker, and a chloramphenicol-resistance gene allowing positive selection of both oriT and sacB. Introduction of plasmid-borne DNA into the chromosome was achieved in several steps. The DNA to be exchanged was first cloned into the new ColE1-type vectors. After insertion of the oriT and sacB sequences, these plasmid were conjugally transferred into P. aeruginosa and plasmid integrants were selected. Plating on sucrose-containing medium allowed positive selection for both plasmid excision and curing since Pseudomonas aeruginosa strains containing the sacB gene in single- or multiple copy were highly sensitive to 5% sucrose in rich medium. This procedure was successfully used to introduce an agmR mutation into P. aeruginosa wild-type strain PAO1 and should allow the exchange of any DNA segment into any non-essential regions of the P. aeruginosa chromosome.

BACKGROUND: Updated information on the epidemiology of dementia due to Alzheimer's disease (AD) is needed to ensure that adequate resources are available to meet current and future healthcare needs. We conducted a systematic review and meta-analysis of the incidence and prevalence of AD. METHODS: The MEDLINE and EMBASE databases were searched from 1985 to 2012, as well as the reference lists of selected articles. Included articles had to provide an original population-based estimate for the incidence and/or prevalence of AD. Two individuals independently performed abstract and full-text reviews, data extraction and quality assessments. Random-effects models were employed to generate pooled estimates stratified by age, sex, diagnostic criteria, location (i.e., continent) and time (i.e., when the study was done). RESULTS: Of 16,066 abstracts screened, 707 articles were selected for full-text review. A total of 119 studies met the inclusion criteria. In community settings, the overall point prevalence of dementia due to AD among individuals 60+ was 40.2 per 1000 persons (CI95%: 29.1-55.6), and pooled annual period prevalence was 30.4 per 1000 persons (CI95%: 15.6-59.1). In community settings, the overall pooled annual incidence proportion of dementia due to AD among individuals 60+ was 34.1 per 1000 persons (CI95%: 16.4-70.9), and the incidence rate was 15.8 per 1000 person-years (CI95%: 12.9-19.4). Estimates varied significantly with age, diagnostic criteria used and location (i.e., continent). CONCLUSIONS: The burden of AD dementia is substantial. Significant gaps in our understanding of its epidemiology were identified, even in a high-income country such as Canada. Future studies should assess the impact of using such newer clinical diagnostic criteria for AD dementia such as those of the National Institute on Aging-Alzheimer's Association and/or incorporate validated biomarkers to confirm the presence of Alzheimer pathology to produce more precise estimates of the global burden of AD.

Previous studies have reported converging lung cancer rates between sexes. We examine lung cancer incidence rates in young women vs. young men in 40 countries across five continents. Lung and bronchial cancer cases by 5-year age group (ages 30-64) and 5-year calendar period (1993-2012) were extracted from Cancer Incidence in Five Continents. Female-to-male incidence rate ratios (IRRs) and 95% confidence intervals (95%CIs) were calculated by age group and birth cohort. Among men, age-specific lung cancer incidence rates generally decreased in all countries, while in women the rates varied across countries with the trends in most countries stable or declining, albeit at a slower pace compared to those in men. As a result, the female-to-male IRRs increased among recent birth cohorts, with IRRs significantly greater than unity in Canada, Denmark, Germany, New Zealand, the Netherlands and the United States. For example, the IRRs in ages 45-49 year in the Netherlands increased from 0.7 (95% CI: 0.6-0.8) to 1.5 (95% CI: 1.4-1.7) in those born circa 1948 and 1963, respectively. Similar patterns, though nonsignificant, were found in 23 additional countries. These crossovers were largely driven by increasing adenocarcinoma incidence rates in women. For those countries with historical smoking data, smoking prevalence in women approached, but rarely exceeded, those of men. In conclusion, the emerging higher lung cancer incidence rates in young women compared to young men is widespread and not fully explained by sex differences in smoking patterns. Future studies are needed to identify reasons for the elevated incidence of lung cancer among young women.

OBJECTIVE: The objective of this study was to establish the effectiveness of interventions to reduce frequent emergency department (ED) use among a general adult high ED-use population. METHODS: Systematic review of the literature from 1950-January 2015. Studies were included if they: had a control group (controlled trials or comparative cohort studies), were set in an ED or acute care facility, and examined the impact of an intervention to reduce frequent ED use in a general adult population. Studies reporting non-original data or focused on a specific patient population were excluded. Study design, patient population, intervention, the frequency of ED visits, and costs of frequent ED use and/or interventions were extracted and narratively synthesized. RESULTS: Among 17 included articles, three intervention categories were identified: case management (n = 12), individualized care plans (n = 3), and information sharing (n = 2). Ten studies examining case management reported reductions in mean (-0.66 to -37) or median (-0.1 to -20) number of ED visits after 12-months; one study reported an increase in mean ED visits (+2.79); and one reported no change. Of these, 6 studies also reported reduced hospital costs. Only 1 study evaluating individualized care plans examined ED utilization and found no change in median ED visits post-intervention. Costs following individualized care plans were also only evaluated in 1 study, which reported savings in hospital costs of $742/patient. Evidence was mixed regarding information sharing: 1 study reported no change in mean ED visits and did not examine costs; whereas the other reported a decrease in mean ED visits (-16.9) and ED cost savings of $15,513/patient. CONCLUSIONS: The impact of all three frequent-user interventions was modest. Case management had the most rigorous evidence base, yielded moderate cost savings, but with variable reductions in ED use. Future studies evaluating non-traditional interventions, tailoring to patient subgroups or socio-cultural contexts, are warranted.

A population-based active-surveillance study of the Calgary Health Region (population, 929,656) was conducted from May 1999 to April 2000, to define the epidemiology of invasive Staphylococcus aureus (ISA) infections. The annual incidence was 28.4 cases/100,000 population; 46% were classified as nosocomial. Infection was most common in people at the extremes of the age spectrum and in males. Several conditions were associated with acquisition of ISA infection, and the highest risk was observed in persons undergoing hemodialysis or peritoneal dialysis and in persons infected with human immunodeficiency virus. Forty-six patients (19%) died. Significant independent risk factors for mortality included positive blood-culture result, respiratory focus, empirical antibiotic therapy, and older age. A higher systolic blood pressure at presentation was associated with reduced case-fatality rate. ISA infections are common, with several definable groups of patients at increased risk for acquisition and death from these infections. This study provides important data on the burden of ISA disease and identifies risk groups that may potentially benefit from preventive efforts.

RATIONALE: The diagnostic usefulness and safety of transbronchial lung cryobiopsy for the evaluation of interstitial lung disease remain unclear. OBJECTIVES: This systematic review and metaanalysis aims to establish the diagnostic accuracy and yield of transbronchial cryobiopsy for interstitial lung diseases. METHODS: We searched MedLine, EMBASE, Cochrane Central Register of Controlled Trials, and conference proceedings to identify studies assessing the diagnostic accuracy (compared with surgical biopsy) or yield of transbronchial lung cryobiopsy for interstitial lung disease (from database inception to January 2016). The diagnostic accuracy and yield were quantified and stratified by the method of diagnosis determination (histologic interpretation in isolation vs. incorporation within a multidisciplinary discussion). The frequency of procedure-related complications was also assessed from these reports. For full-text studies, random-effects models were used to calculate pooled estimates of diagnostic accuracy, yield, and complication frequency. MEASUREMENTS AND MAIN RESULTS: Of 900 citations, 11 studies were selected for inclusion in this systematic review (7 full text, 4 abstracts). The selected studies reported on a total of 731 patients. No studies reported the diagnostic accuracy of transbronchial cryobiopsy. Diagnostic yield ranged from 74 to 98% when transbronchial cryobiopsy findings were interpreted in isolation, with a pooled estimate of 83% (95% confidence interval [CI], 73-94). Diagnostic yield ranged from 51 to 98% when transbronchial cryobiopsy was reviewed within a multidisciplinary discussion, with a pooled estimate of 79% (95% CI, 65-93). Pooled estimates for pneumothorax and moderate/severe bleeding were 12% (95% CI, 3-21) and 39% (95% CI, 3-76), respectively. CONCLUSIONS: The diagnostic accuracy of transbronchial lung cryobiopsy cannot be determined given the absence of studies directly comparing cryobiopsy diagnoses with diagnoses derived from surgical lung biopsies interpreted within multidisciplinary discussions. The histopathological and multidisciplinary discussion-based diagnostic yield of transbronchial cryobiopsy appears high, but with variable frequencies of complications dominated by pneumothorax and moderate-to-severe hemorrhage.