Elie A Akl

American University of Beirut, Beyrouth, Beyrouth, Lebanon

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Publications (199)1071.38 Total impact

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    ABSTRACT: Anticoagulation may improve survival in patients with cancer through an antitumor effect in addition to the perceived antithrombotic effect. To evaluate the efficacy and safety of parenteral anticoagulants in ambulatory patients with cancer who, typically, are undergoing chemotherapy, hormonal therapy or radiotherapy, but otherwise have no standard therapeutic or prophylactic indication for anticoagulation. A comprehensive search included (1) an electronic search (February 2013) of the following databases: Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 1), MEDLINE (1966 to February 2013; accessed via OVID) and EMBASE(1980 to February 2013; accessed via OVID); (2) handsearching of conference proceedings; (3) checking of references of included studies; (4) use of the 'related citation' feature in PubMed and (5) a search for ongoing studies. Randomized controlled trials (RCTs) assessing the benefits and harms of parenteral anticoagulation in ambulatory patients with cancer. Typically, these patients are undergoing chemotherapy, hormonal therapy or radiotherapy, but otherwise have no standard therapeutic or prophylactic indication for anticoagulation. Using a standardized form we extracted data in duplicate on methodological quality, participants, interventions and outcomes of interest including all-cause mortality, symptomatic venous thromboembolism (VTE), symptomatic deep vein thrombosis (DVT), symptomatic pulmonary embolism (PE), arterial thrombosis (e.g. stroke, myocardial infarction), major bleeding, minor bleeding and quality of life. Of 9559 identified citations, 15 RCTs fulfilled the eligibility criteria. These trials enrolled 7622 participants for whom follow-up data were available. In all included RCTs the intervention consisted of heparin (either unfractionated heparin or low molecular weight heparin). Overall, heparin may have a small effect on mortality at 12 months and 24 months (risk ratio (RR) 0.97; 95% confidence interval (CI) 0.92 to 1.01 and RR 0.95; 95% CI 0.90 to 1.00, respectively). Heparin therapy was associated with a statistically and clinically important reduction in venous thromboembolism (RR 0.56; 95% CI 0.42 to 0.74) and a clinically important increase in the risk of minor bleeding (RR 1.32; 95% 1.02 to 1.71). Results failed to show or to exclude a beneficial or detrimental effect of heparin on major bleeding (RR 1.14; 95% CI 0.70 to 1.85) or quality of life. Our confidence in the effect estimates (i.e. quality of evidence) was high for symptomatic venous thromboembolism, moderate for mortality, major bleeding and minor bleeding, and low for quality of life. Heparin may have a small effect on mortality at 12 months and 24 months. It is associated with a reduction in venous thromboembolism and a likely increase in minor bleeding. Future research should further investigate the survival benefit of different types of anticoagulants in patients with different types and stages of cancer. The decision for a patient with cancer to start heparin therapy for survival benefit should balance the benefits and downsides, and should integrate the patient's values and preferences.
    Cochrane database of systematic reviews (Online) 12/2014; 12:CD006652. · 5.70 Impact Factor
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    ABSTRACT: Background There is no consensus on how authors conducting meta-analysis should deal with trial participants with missing outcome data. The objectives of this study are to assess in Cochrane and non-Cochrane systematic reviews: (1) which categories of trial participants the systematic review authors consider as having missing participant data (MPD), (2) how trialists reported on participants with missing outcome data in trials, (3) whether systematic reviewer authors actually dealt with MPD in their meta-analyses of dichotomous outcomes consistently with their reported methods, and (4) the impact of different methods of dealing with MPD on pooled effect estimates in meta-analyses of dichotomous outcomes. Methods/design We will conduct a methodological study of Cochrane and non-Cochrane systematic reviews. Eligible systematic reviews will include a group-level meta-analysis of a patient-important dichotomous efficacy outcome, with a statistically significant effect estimate. Teams of two reviewers will determine eligibility and subsequently extract information from each eligible systematic review in duplicate and independently, using standardized, pre-piloted forms. The teams will then use a similar process to extract information from the trials included in the meta-analyses of interest. We will assess first which categories of trial participants the systematic reviewers consider as having MPD. Second, we will assess how trialists reported on participants with missing outcome data in trials. Third, we will compare what systematic reviewers report having done, and what they actually did, in dealing with MPD in their meta-analysis. Fourth, we will conduct imputation studies to assess the effects of different methods of dealing with MPD on the pooled effect estimates of meta-analyses. We will specifically calculate for each method (1) the percentage of systematic reviews that lose statistical significance and (2) the mean change of effect estimates across systematic reviews. Discussion The impact of different methods of dealing with MPD on pooled effect estimates will help judge the associated risk of bias in systematic reviews. Our findings will inform recommendations regarding what assumptions for MPD should be used to test the robustness of meta-analytical results.
    Systematic Reviews. 11/2014; 3(1):137.
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    ABSTRACT: Background:Bridging the gap between clinical research and everyday healthcare practice requires effective communication strategies. To address current shortcomings in conveying practice recommendations and supporting evidence, we are creating and testing presentation formats for clinical practice guidelines (CPGs). Methods:We carried out multiple cycles of brainstorming and sketching, developing a prototype. Physicians participating in the user testing viewed CPG formats linked to clinical scenarios and engaged in semi-structured interviews applying a think-aloud method for exploring important aspects of user experience. Results:We developed a multilayered presentation format that allows clinicians to successively view more in depth information. Starting with the recommendations clinicians can on demand access a rationale and a key information section containing statements on quality of the evidence, balance between desirable and undesirable consequences, values and preferences, and resource considerations. We collected feedback from 27 stakeholders and performed user testing with 47 practicing physicians from six countries. Advisory group feedback and user testing of the first version revealed problems with conceptual understanding of underlying CPG methodology, as well as difficulties with the complexity of the layout and content. Extensive revisions made before the second round of user testing resulted in most participants expressing overall satisfaction with the final presentation format. Conclusion:We have developed an electronic multilayered CPG format that enhances the usability of CPGs for front-line clinicians. We have implemented the format in electronic guideline tools which guideline organizations can now use when authoring and publishing their guidelines.
    Chest 10/2014; · 7.13 Impact Factor
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    ABSTRACT: Faculty productivity is essential for academic medical centers striving to achieve excellence and national recognition. The objective of this study was to evaluate whether and how academic Departments of Medicine in the United States measure faculty productivity for the purpose of salary compensation.
    BMC Medical Education 09/2014; 14(1):205. · 1.41 Impact Factor
  • Elie A Akl, Gordon H Guyatt
    Annals of internal medicine 09/2014; 161(6):JC9. · 13.98 Impact Factor
  • Elie A Akl, Gordon H Guyatt
    Annals of internal medicine 09/2014; 161(6):JC8. · 13.98 Impact Factor
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    ABSTRACT: Systematic reviews can offer policymakers and stakeholders concise, transparent, and relevant evidence pertaining to pressing policy priorities to help inform the decision-making process. The production and the use of systematic reviews are specifically limited in the Eastern Mediterranean region. The extent to which published systematic reviews address policy priorities in the region is still unknown. This situational analysis exercise aims at assessing the extent to which published systematic reviews address policy priorities identified by policymakers and stakeholders in Eastern Mediterranean region countries. It also provides an overview about the state of systematic review production in the region and identifies knowledge gaps.
    Health research policy and systems / BioMed Central. 08/2014; 12(1):48.
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    ABSTRACT: OBJECTIVE: To investigate the planning of subgroup analyses in protocols of randomised controlled trials and the agreement with corresponding full journal publications. DESIGN: Cohort of protocols of randomised controlled trial and subsequent full journal publications. SETTING: Six research ethics committees in Switzerland, Germany, and Canada. DATA SOURCES: 894 protocols of randomised controlled trial involving patients approved by participating research ethics committees between 2000 and 2003 and 515 subsequent full journal publications. RESULTS: Of 894 protocols of randomised controlled trials, 252 (28.2%) included one or more planned subgroup analyses. Of those, 17 (6.7%) provided a clear hypothesis for at least one subgroup analysis, 10 (4.0%) anticipated the direction of a subgroup effect, and 87 (34.5%) planned a statistical test for interaction. Industry sponsored trials more often planned subgroup analyses compared with investigator sponsored trials (195/551 (35.4%) v 57/343 (16.6%), P<0.001). Of 515 identified journal publications, 246 (47.8%) reported at least one subgroup analysis. In 81 (32.9%) of the 246 publications reporting subgroup analyses, authors stated that subgroup analyses were prespecified, but this was not supported by 28 (34.6%) corresponding protocols. In 86 publications, authors claimed a subgroup effect, but only 36 (41.9%) corresponding protocols reported a planned subgroup analysis. CONCLUSIONS: Subgroup analyses are insufficiently described in the protocols of randomised controlled trials submitted to research ethics committees, and investigators rarely specify the anticipated direction of subgroup effects. More than one third of statements in publications of randomised controlled trials about subgroup prespecification had no documentation in the corresponding protocols. Definitive judgments regarding credibility of claimed subgroup effects are not possible without access to protocols and analysis plans of randomised controlled trials.
    BMJ: British medical journal 07/2014; · 16.30 Impact Factor
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    ABSTRACT: The American College of Chest Physicians Antithrombotic Guidelines ninth iteration placed restrictions on panelists with recommendations on which they disclosed a primary conflict of interest (COI). We aimed to describe panelists' financial and intellectual COI and evaluate to what extent, beyond assessing financial COI, assessing intellectual COI affected COI management.
    Journal of clinical epidemiology. 06/2014;
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    ABSTRACT: Adaptation of guidelines for use at the national or local level can facilitate their implementation. We developed and evaluated an adaptation process in adherence with standards for trustworthy guidelines and the GRADE methodology aiming for efficiency and transparency. This is the first in a series of four articles describing our adaptation of the 9th iteration of the American College of Chest Physicians Antithrombotic Therapy and Prevention of Thrombosis for a Norwegian setting. Informed by the ADAPTE framework, we developed a 5-step adaptation process customized to guidelines developed with GRADE: 1) planning, 2) initial assessment of the recommendations, 3) modification, 4) publication, and 5) evaluation. We developed a taxonomy for describing how and why recommendations from the parent guideline were modified. We applied a mixed-methods, case-study design for evaluation of the process. We published the adapted guideline November 2013 in a novel multilayered format. The taxonomy for adaptation facilitated transparency of the modification process for both the guideline developers and end-users. We excluded 30 and modified 131 of the 333 original recommendations according to the taxonomy and developed 8 new recommendations. Unforeseen obstacles related to acquiring a licensing agreement and procuring a publisher resulted in a 9-month delay. We propose modifications of the adaptation process to overcome these obstacles in the future. This case study demonstrates the feasibility of our novel adaptation process. Replication is needed to further validate the usefulness of the process in increasing the organizational and methodological efficiency of guideline adaptation.
    Chest 04/2014; · 7.13 Impact Factor
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    ABSTRACT: The Antithrombotic Therapy and the Prevention of Thrombosis, 9th Edition: American College of Chest Physicians Evidence-based Guidelines (AT9) represent trustworthy international guidelines for antithrombotic treatment and thromboprophylaxis. Here, we describe major changes to the format and content resulting from applying new strategies for guideline adaptation and dissemination. A Norwegian guideline panel of 46 experts completed a structured and systematic adaptation process, updating the recommendations based on new evidence, and rewrote the recommendations in an electronic multilayered presentation format. We published the adapted guideline using a web-based authoring and publication platform (MAGICapp at www.magicapp.org/public). We applied a novel presentation format to 333 recommendations from 11 of the 15 management chapters in AT9, condensed and restructured into 249 recommendations in a multilayered format. We added additional relevant information, such as 29 best practice statements about new oral anticoagulants and practical information sections for 121 recommendations. Common reasons for modifications included feasibility of the recommendations in a national context, disagreement with applied baseline risk estimates and re-evaluating the balance between the benefits and harms of interventions in relation to assumed typical patient preferences and values. The adapted guideline was published and disseminated online in November 2013. New strategies for adapting, updating and disseminating trustworthy guidelines proved feasible and will provide Norwegian health care professionals and patients with up to date guidance tailored to national circumstances.
    Chest 04/2014; · 7.13 Impact Factor
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    ABSTRACT: The discontinuation of randomized clinical trials (RCTs) raises ethical concerns and often wastes scarce research resources. The epidemiology of discontinued RCTs, however, remains unclear. To determine the prevalence, characteristics, and publication history of discontinued RCTs and to investigate factors associated with RCT discontinuation due to poor recruitment and with nonpublication. Retrospective cohort of RCTs based on archived protocols approved by 6 research ethics committees in Switzerland, Germany, and Canada between 2000 and 2003. We recorded trial characteristics and planned recruitment from included protocols. Last follow-up of RCTs was April 27, 2013. Completion status, reported reasons for discontinuation, and publication status of RCTs as determined by correspondence with the research ethics committees, literature searches, and investigator surveys. After a median follow-up of 11.6 years (range, 8.8-12.6 years), 253 of 1017 included RCTs were discontinued (24.9% [95% CI, 22.3%-27.6%]). Only 96 of 253 discontinuations (37.9% [95% CI, 32.0%-44.3%]) were reported to ethics committees. The most frequent reason for discontinuation was poor recruitment (101/1017; 9.9% [95% CI, 8.2%-12.0%]). In multivariable analysis, industry sponsorship vs investigator sponsorship (8.4% vs 26.5%; odds ratio [OR], 0.25 [95% CI, 0.15-0.43]; P < .001) and a larger planned sample size in increments of 100 (-0.7%; OR, 0.96 [95% CI, 0.92-1.00]; P = .04) were associated with lower rates of discontinuation due to poor recruitment. Discontinued trials were more likely to remain unpublished than completed trials (55.1% vs 33.6%; OR, 3.19 [95% CI, 2.29-4.43]; P < .001). In this sample of trials based on RCT protocols from 6 research ethics committees, discontinuation was common, with poor recruitment being the most frequently reported reason. Greater efforts are needed to ensure the reporting of trial discontinuation to research ethics committees and the publication of results of discontinued trials.
    JAMA The Journal of the American Medical Association 03/2014; 311(10):1045-51. · 29.98 Impact Factor
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    ABSTRACT: BACKGROUND: We previously developed an approach to address the impact of missing participant data in meta-analyses of continuous variables in trials that used the same measurement instrument. We extend this approach to meta-analyses including trials that use different instruments to measure the same construct. METHODS: We reviewed the available literature, conducted an iterative consultative process, and developed an approach involving a complete-case analysis complemented by sensitivity analyses that apply a series of increasingly stringent assumptions about results in patients with missing continuous outcome data. RESULTS: Our approach involves choosing the reference measurement instrument; converting scores from different instruments to the units of the reference instrument; developing four successively more stringent imputation strategies for addressing missing participant data; calculating a pooled mean difference for the complete-case analysis and imputation strategies; calculating the proportion of patients who experienced an important treatment effect; and judging the impact of the imputation strategies on the confidence in the estimate of effect. We applied our approach to an example systematic review of respiratory rehabilitation for chronic obstructive pulmonary disease. CONCLUSIONS: Our extended approach provides quantitative guidance for addressing missing participant data in systematic reviews of trials using different instruments to measure the same construct.
    Journal of Clinical Epidemiology 03/2014; · 5.48 Impact Factor
  • C Kearon, Elie A Akl
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    ABSTRACT: It takes about 3 months to complete "active treatment" of venous thromboembolism (VTE), with further treatment serving to prevent new episodes of thrombosis ("pure secondary prevention"). Consequently, VTE should generally be treated for either 3 months or indefinitely (see text for exceptions). The decision to stop anticoagulants at 3 months or to treat indefinitely is dominated by the long-term risk of recurrence, and secondarily influenced by the risk of bleeding and by patient preference. VTE provoked by a reversible risk factor, or a first unprovoked isolated distal (calf) deep vein thrombosis (DVT), has a low risk of recurrence and is usually treated for 3 months. VTE associated with active cancer, or a second unprovoked VTE, has a high risk of recurrence and is usually treated indefinitely. The decision to stop anticoagulants at 3 months or to treat indefinitely is more finely balanced after a first unprovoked proximal DVT or pulmonary embolism (PE). Indefinite anticoagulation is often chosen if there is a low risk of bleeding, whereas anticoagulation is usually stopped at 3 months if there is a high risk of bleeding. The decision to continue anticoagulation indefinitely after a first unprovoked proximal DVT or PE is strengthened if the patient is male, the index event was PE rather than DVT, and/or D-dimer testing is positive 1 month after stopping anticoagulant therapy.
    Blood 02/2014; · 9.78 Impact Factor
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    ABSTRACT: Although even randomization (that is, approximately 1:1 randomization ratio in study arms) provides the greatest statistical power, designed uneven randomization (DUR), (for example, 1:2 or 1:3) is used to increase participation rates. Until now, no convincing data exists addressing the impact of DUR on participation rates in trials. The objective of this study is to evaluate the epidemiology and to explore factors associated with DUR. We will search for reports of RCTs published within two years in 25 general medical journals with the highest impact factor according to the Journal Citation Report (JCR)-2010. Teams of two reviewers will determine eligibility and extract relevant information from eligible RCTs in duplicate and using standardized forms. We will report the prevalence of DUR trials, the reported reasons for using DUR, and perform a linear regression analysis to estimate the association between the randomization ratio and the associated factors, including participation rate, type of informed consent, clinical area, and so on. A clearer understanding of RCTs with DUR and its association with factors in trials, for example, participation rate, can optimize trial design and may have important implications for both researchers and users of the medical literature.
    Trials 01/2014; 15(1):33. · 2.21 Impact Factor
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    ABSTRACT: Background Viral hepatitis B and C (HBV, HCV) disproportionately affect people who inject drugs (PWID) across the world. To date there has been little global action focusing on prevention, care and treatment of HBV and HCV among PWID. Here we report on the development process and discuss the implications of evidence informed WHO Guidelines for the Prevention of HBV and HCV in PWID. Methods The World Health Organization (WHO) convened a Guideline Development Panel to develop recommendations on the prevention of HBV and HCV among PWID. The process followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. It included the development of PICO (Population, Interventions, Comparator, Outcomes) questions and conducting systematic reviews. Quality of evidence was classified into 4 levels: high, moderate, low, and very low. In the process of moving from evidence to recommendations, the following were considered: quality of evidence, balance of benefits and harms, community values and preferences and resource use. Results The WHO recommendations include the following for working with PWID: offer the rapid HBV vaccination regimen; offer incentives to increase uptake and completion of the HBV vaccine schedule; needle and syringe programs should also provide low dead-space syringes for distribution; and offer peer interventions to reduce the incidence of viral hepatitis. This guideline complements other WHO documents regarding PWID, including HIV prevention initiatives such as needle and syringe programs and opioid substitution therapy. Conclusion This guidance offers a first step in the prevention of HBV and HCV among PWID. However, the lack of high quality evidence in this area necessitates further research and resources for implementation.
    The International journal on drug policy 01/2014; · 2.54 Impact Factor
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    ABSTRACT: OBJECTIVE::To investigate the prevalence of discontinuation and nonpublication of surgical versus medical randomized controlled trials (RCTs) and to explore risk factors for discontinuation and nonpublication of surgical RCTs. BACKGROUND::Trial discontinuation has significant scientific, ethical, and economic implications. To date, the prevalence of discontinuation of surgical RCTs is unknown. METHODS::All RCT protocols approved between 2000 and 2003 by 6 ethics committees in Canada, Germany, and Switzerland were screened. Baseline characteristics were collected and, if published, full reports retrieved. Risk factors for early discontinuation for slow recruitment and nonpublication were explored using multivariable logistic regression analyses. RESULTS::In total, 863 RCT protocols involving adult patients were identified, 127 in surgery (15%) and 736 in medicine (85%). Surgical trials were discontinued for any reason more often than medical trials [43% vs 27%, risk difference 16% (95% confidence interval [CI]: 5%-26%); P = 0.001] and more often discontinued for slow recruitment [18% vs 11%, risk difference 8% (95% CI: 0.1%-16%); P = 0.020]. The percentage of trials not published as full journal article was similar in surgical and medical trials (44% vs 40%, risk difference 4% (95% CI: -5% to 14%); P = 0.373). Discontinuation of surgical trials was a strong risk factor for nonpublication (odds ratio = 4.18, 95% CI: 1.45-12.06; P = 0.008). CONCLUSIONS::Discontinuation and nonpublication rates were substantial in surgical RCTs and trial discontinuation was strongly associated with nonpublication. These findings need to be taken into account when interpreting surgical literature. Surgical trialists should consider feasibility studies before embarking on full-scale trials.
    Annals of Surgery 01/2014; · 6.33 Impact Factor
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    ABSTRACT: There is conflicting evidence about the association between low vitamin D levels in children and development of asthma in later life. The objective of this study was to systematically review the evidence for an epidemiological association between low serum levels of vitamin D and the diagnosis of asthma in children.
    Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology. 01/2014; 10(1):31.
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    ABSTRACT: Pharmaceutical company representatives likely influence the prescribing habits and professional behaviour of physicians.
    BMJ Open 01/2014; 4(7):e004880. · 2.06 Impact Factor
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    ABSTRACT: Venous thromboembolism (VTE) is a major disease associated with short-term and long-term morbidity and mortality. Patients with a VTE provoked by surgery or immobilisation are at low risk of recurrence and do not require long-term anticoagulation; those with a VTE and metastatic cancer are at high risk of recurrence and require lifetime thromboprophylaxis. In those at intermediate risk of recurrence, it remains controversial whether prolonging anticoagulation and thus incurring treatment burden and bleeding risk is warranted.
    BMJ Open 01/2014; 4(7):e005674. · 2.06 Impact Factor

Publication Stats

4k Citations
1,071.38 Total Impact Points

Institutions

  • 2010–2014
    • American University of Beirut
      • Department of Internal Medicine
      Beyrouth, Beyrouth, Lebanon
    • State University of New York
      New York City, New York, United States
    • Boston University
      • Department of Medicine
      Boston, MA, United States
    • Lebanese American University
      Beyrouth, Beyrouth, Lebanon
  • 2004–2014
    • McMaster University
      • Department of Clinical Epidemiology and Biostatistics
      Hamilton, Ontario, Canada
  • 2013
    • Imperial College London
      • Department of Primary Care and Public Health
      London, ENG, United Kingdom
    • Jagiellonian University
      • II Department of Internal Medicine
      Kraków, Lesser Poland Voivodeship, Poland
    • Vanderbilt University
      • Vanderbilt Center for Evidence-based Medicine
      Nashville, MI, United States
  • 2004–2013
    • University at Buffalo, The State University of New York
      • • Department of Medicine
      • • Department of Sociology
      Buffalo, New York, United States
  • 2012
    • Jewish General Hospital
      Montréal, Quebec, Canada
    • Stanford University
      • Stanford Stroke Center
      Stanford, CA, United States
    • The University of Western Ontario
      London, Ontario, Canada
    • Kaiser Permanente
      • Center for Health Research (Oregon, Hawaii, and Georgia)
      Oakland, CA, United States
  • 2011
    • Universitätsklinikum Freiburg
      • Institute of Medical Biometry and Statistics
      Freiburg an der Elbe, Lower Saxony, Germany
  • 2009–2011
    • Norwegian Knowledge Centre for the Health Services
      Kristiania (historical), Oslo County, Norway
    • Erie County Medical Center
      New York City, New York, United States
  • 2006–2009
    • Istituto Regina Elena - Istituti Fisioterapici Ospitalieri
      Roma, Latium, Italy
  • 2007
    • University of Barcelona
      • Departament de Medicina
      Barcelona, Catalonia, Spain
  • 2005–2006
    • Mayo Foundation for Medical Education and Research
      • Department of Medicine
      Scottsdale, AZ, United States