Timothy J Wilt

Massachusetts General Hospital, Boston, Massachusetts, United States

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Publications (265)1483.2 Total impact

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    ABSTRACT: Prostate cancer is a common malignancy in men and the worldwide burden of this disease is rising. Lifestyle modifications such as smoking cessation, exercise, and weight control offer opportunities to reduce the risk of developing prostate cancer. Early detection of prostate cancer by prostate-specific antigen (PSA) screening is controversial, but changes in the PSA threshold, frequency of screening, and the use of other biomarkers have the potential to minimise the overdiagnosis associated with PSA screening. Several new biomarkers for individuals with raised PSA concentrations or those diagnosed with prostate cancer are likely to identify individuals who can be spared aggressive treatment. Several pharmacological agents such as 5α-reductase inhibitors and aspirin could prevent development of prostate cancer. In this Review, we discuss the present evidence and research questions regarding prevention, early detection of prostate cancer, and management of men either at high risk of prostate cancer or diagnosed with low-grade prostate cancer.
    The Lancet Oncology 10/2014; 15(11):e484-e492. · 25.12 Impact Factor
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    ABSTRACT: Objective. Evaluate the evidence for effects of inpatient antimicrobial stewardship programs (ASPs) on patient, prescribing, and microbial outcomes. Design. Systematic review. Methods. Search of MEDLINE (2000 through November 2013), Cochrane Library, and reference lists of relevant studies. We included English language studies with patient populations relevant to the United States (ie, infectious conditions and prescriptions required for antimicrobials) that evaluated ASP interventions and reported outcomes of interest. Study characteristics and outcomes data were extracted and reviewed by investigators and trained research personnel. Results. Few intervention types (eg, audit and feedback, guideline implementation, and decision support) substantially impacted patient outcomes, including mortality, length of stay, readmission, or incidence of Clostridium difficile infection. However, most interventions were not powered adequately to demonstrate impacts on patient outcomes. Most interventions were associated with improved prescribing patterns as measured by decreased antimicrobial use or increased appropriate use. Where reported, ASPs were generally associated with improvements in microbial outcomes, including institutional resistance patterns or resistance in the study population. Few data were provided on harms, sustainability, or key intervention components. Studies were typically of short duration, low in methodological quality, and varied in study design, populations enrolled, hospital setting, ASP intent, intervention composition and implementation, comparison group, and outcomes assessed. Conclusions. Numerous studies suggest that ASPs can improve prescribing and microbial outcomes. Strength of evidence was low, and most studies were not designed adequately to detect improvements in mortality or other patient outcomes, but obvious adverse effects on patient outcomes were not reported.
    10/2014; 35(10):1209-1228.
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    ABSTRACT: The American College of Physicians recently published a guideline on screening for CKD that recommends against screening for CKD in asymptomatic adults without risk factors. The generally accepted criteria for population-based screening for disease state that screening should improve important clinical outcomes while limiting harms for those individuals screened. However, CKD screening does not meet these criteria. There is currently no evidence evaluating or demonstrating benefits for providing early treatment for patients identified via screening who do not have risk factors. On the other hand, harms are associated with the screening and include false-positive results, unnecessary testing and treatment, and disease labeling.
    Clinical journal of the American Society of Nephrology : CJASN. 09/2014;
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    ABSTRACT: The Agency for Healthcare Research and Quality (AHRQ) has funded systematic reviews of comparative effectiveness research in 17 areas over the last 10 years as part of a federal mandate. These reviews provide a reliable and unbiased source of comprehensive information about the effectiveness and risks of treatment alternatives for patients and clinicians. This article describes comparative effectiveness research, provides an overview of how physicians can use it in clinical practice, and references important contributions made by the Minnesota Evidence-based Practice Center.
    Minnesota medicine 08/2014; 97(8):49-51.
  • Amir Qaseem, Timothy Wilt, Thomas D Denberg
    Annals of internal medicine 07/2014; 161(1):83-84. · 13.98 Impact Factor
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    ABSTRACT: Pelvic examination is often included in well-woman visits even when cervical cancer screening is not required.
    Annals of internal medicine 07/2014; 161(1):46-53. · 13.98 Impact Factor
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    ABSTRACT: Behavioral change is critical for improving health outcomes in patients with chronic obstructive pulmonary disease. An educational approach alone is insufficient; changes in behavior, especially the acquisition of self-care skills, are also required. There is mounting evidence that embedding collaborative self-management (CSM) within existing health care systems provides an effective model to meet these needs. CSM should be integrated with pulmonary rehabilitation programs, one of the main goals of which is to induce long-term changes in behavior. More research is needed to evaluate the effectiveness of assimilating CSM into primary care, patient-centered medical homes, and palliative care teams.
    Clinics in chest medicine. 06/2014; 35(2):337-351.
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    ABSTRACT: Family and caregiver interventions typically aim to develop family members' coping and caregiving skills and to reduce caregiver burden. We conducted a systematic review of published randomized controlled trials (RCTs) evaluating whether family-involved interventions improve patient outcomes among adults with cancer.
    Journal of general internal medicine. 05/2014;
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    ABSTRACT: Tissue-preserving focal therapies, such as brachytherapy, cryotherapy, high-intensity focused ultrasound and photodynamic therapy, aim to target individual cancer lesions rather than the whole prostate. These treatments have emerged as potential interventions for localized prostate cancer to reduce treatment-related adverse-effects associated with whole-gland treatments, such as radical prostatectomy and radiotherapy. In this article, the Prostate Cancer RCT Consensus Group propose that a novel cohort-embedded randomized controlled trial (RCT) would provide a means to study men with clinically significant localized disease, which we defined on the basis of PSA level (≤15 ng/ml or ≤20 ng/ml), Gleason grade (Gleason pattern ≤4 + 4 or ≤4 + 3) and stage (≤cT2cN0M0). This RCT should recruit men who stand to benefit from treatment, with the control arm being whole-gland surgery or radiotherapy. Composite outcomes measuring rates of local and systemic salvage therapies at 3-5 years might best constitute the basis of the primary outcome on which to change practice.
    Nature Reviews Clinical Oncology 04/2014; · 15.03 Impact Factor
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    CancerSpectrum Knowledge Environment 03/2014; · 14.07 Impact Factor
  • John M Hollingsworth, Timothy J Wilt
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    ABSTRACT: Benign prostatic hyperplasia (BPH) is a highly prevalent and costly condition that affects older men worldwide. Many affected men develop lower urinary tract symptoms, which can have a negative impact on their quality of life. In the past, transurethral resection of the prostate (TURP) was the mainstay of treatment. However, several efficacious drug treatments have been developed, which have transformed BPH from an acute surgical entity to a chronic medical condition. Specifically, multiple clinical trials have shown that α adrenoceptor antagonists can significantly ameliorate lower urinary tract symptoms. Moreover, 5α reductase inhibitors, alone or combined with an α adrenoceptor antagonist, can reverse the natural course of BPH, reducing the risk of urinary retention and the need for surgical intervention. Newer medical regimens including the use of antimuscarinic agents or phosphodiesterase type 5 inhibitors, have shown promise in men with predominantly storage symptoms and concomitant erectile dysfunction, respectively. For men who do not adequately respond to conservative measures or pharmacotherapy, minimally invasive surgical techniques (such as transurethral needle ablation, microwave thermotherapy, and prostatic urethral lift) may be of benefit, although they lack the durability of TURP. A variety of laser procedures have also been introduced, whose improved hemostatic properties abrogate many of the complications associated with traditional surgery.
    BMJ Clinical Research 01/2014; 349:g4474. · 14.09 Impact Factor
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    ABSTRACT: Nonhealing ulcers affect patient quality of life and impose a substantial financial burden on the health care system. To systematically evaluate benefits and harms of advanced wound care therapies for nonhealing diabetic, venous, and arterial ulcers. MEDLINE (1995 to June 2013), the Cochrane Library, and reference lists. English-language randomized trials reporting ulcer healing or time to complete healing in adults with nonhealing ulcers treated with advanced therapies. Study characteristics, outcomes, adverse events, study quality, and strength of evidence were extracted by trained researchers and confirmed by the principal investigator. For diabetic ulcers, 35 trials (9 therapies) met eligibility criteria. There was moderate-strength evidence for improved healing with a biological skin equivalent (relative risk [RR], 1.58 [95% CI, 1.20 to 2.08]) and negative pressure wound therapy (RR, 1.49 [CI, 1.11 to 2.01]) compared with standard care and low-strength evidence for platelet-derived growth factors and silver cream compared with standard care. For venous ulcers, 20 trials (9 therapies) met eligibility criteria. There was moderate-strength evidence for improved healing with keratinocyte therapy (RR, 1.57 [CI, 1.16 to 2.11]) compared with standard care and low-strength evidence for biological dressing and a biological skin equivalent compared with standard care. One small trial of arterial ulcers reported improved healing with a biological skin equivalent compared with standard care. Overall, strength of evidence was low for ulcer healing and low or insufficient for time to complete healing. Only studies of products approved by the U.S. Food and Drug Administration were reviewed. Studies were predominantly of fair or poor quality. Few trials compared 2 advanced therapies. Compared with standard care, some advanced wound care therapies may improve the proportion of ulcers healed and reduce time to healing, although evidence is limited. Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Quality Enhancement Research Initiative.
    Annals of internal medicine 10/2013; 159(8):532-542. · 13.98 Impact Factor
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    ABSTRACT: The Prostate Cancer Intervention Versus Observation Trial (PIVOT) randomized 731 men with localized prostate cancer to radical prostatectomy or observation. We describe the methods and results for cause-of-death assignments in PIVOT, and compare them to alternative strategies for ascertaining prostate cancer-specific mortality, as well as to the methods and results in the similar Scandinavian Prostate Cancer Group Study 4 (SPCG-4) trial. Three PIVOT Endpoints Committee members, blinded to randomized treatment assignments, reviewed medical records and death certificates when available to assign a cause of death using a primary and a secondary adjudication question. Initial disagreements were resolved through discussion. The level of initial agreement among committee members was examined, as well as guesses at randomized treatment assignments for a convenience sample of cases. Final cause of death determinations were compared to death certificates. Complete agreement on cause of death by all three committee members before any discussion was achieved in 200/354 (56%) cases on the primary and 209/354 (59%) cases on the secondary. However, complete agreement on the primary rose to 306/354 (86%) when 'definite' and 'probably' categories were collapsed, as planned a priori. The three committee members' proportions of correct guesses of randomized treatment assignment were 82/121 (68%), 113/148 (76%), and 99/134 (74%). Using the committee's final adjudications as a gold standard, death certificates had suboptimal sensitivities, specificities, or predictive values depending on how they were used to determine cause of death. There was no separate 'gold standard' by which to judge the accuracy of the final endpoints committee adjudications, and useful death certificates could not be obtained on about a third of PIVOT participants who died. The low level of initial agreement on cause of death among endpoint committee members and the potential for biased determinations due to partial unblinding to treatment assignment raise methodologic concerns about using prostate cancer mortality as an endpoint in clinical trials like PIVOT.
    Clinical Trials 08/2013; · 2.20 Impact Factor
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    ABSTRACT: Primary care providers frequently recommend, administer, or prescribe health care services that are unlikely to benefit their patients. Yet little is known about how to reduce provider overuse behavior. In the absence of a theoretically grounded causal framework, it is difficult to predict the contexts under which different types of interventions to reduce provider overuse will succeed and under which they will fail. In this article, we present a framework based on the theory of planned behavior that is designed to guide overuse research and intervention development. We describe categories of primary care provider beliefs that lead to the formation of intentions to assess the appropriateness of services, and propose factors that may affect whether the presence of assessment intentions results in an appropriate recommendation. Interventions that have been commonly used to address provider overuse behavior are reviewed within the context of the framework.
    Medical Care Research and Review 08/2013; · 3.01 Impact Factor
  • Michael Levitt, Timothy Wilt, Aasma Shaukat
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    ABSTRACT: The majority of the world's adult population and an estimated 80 million Americans are hypolactasic and hence malabsorb ingested lactose. Although lactose malabsorption is easily identified, less readily assessed is the clinically important question of how often does this malabsorption induce symptoms. This review summarizes: (1) knowledge concerning the etiology and diagnosis of hypolactasia and the pathophysiology of the symptoms of lactose malabsorption and (2) the results of well-controlled trials of the symptomatic response of lactose malabsorbers to varying dosages of lactose and the efficacy of therapeutic interventions to alleviate these symptoms. We conclude that the clinical significance of lactose malabsorption has been overestimated by both the lay public and physicians in that commonly ingested doses of lactose (ie, the quantity in a cup of milk) usually do not cause perceptible symptoms when ingested with a meal. Symptoms occur when the lactose dosage exceeds that in a cup of milk or when lactose is ingested without other nutrients. Simple dietary instruction, rather than the use of commercial products to reduce lactose intake, is recommended for the vast majority of lactose-malabsorbing subjects.
    Journal of clinical gastroenterology 04/2013; · 2.21 Impact Factor
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    ABSTRACT: Optimum management to prevent recurrent kidney stones is uncertain. To evaluate the benefits and harms of interventions to prevent recurrent kidney stones. MEDLINE, Cochrane, and other databases through September 2012 and reference lists of systematic reviews and randomized, controlled trials (RCTs). 28 English-language RCTs that studied treatments to prevent recurrent kidney stones and reported stone outcomes. One reviewer extracted data, a second checked accuracy, and 2 independently rated quality and graded strength of evidence. In patients with 1 past calcium stone, low-strength evidence showed that increased fluid intake halved recurrent composite stone risk compared with no treatment (relative risk [RR], 0.45 [95% CI, 0.24 to 0.84]). Low-strength evidence showed that reducing soft-drink consumption decreased recurrent symptomatic stone risk (RR, 0.83 [CI, 0.71 to 0.98]). In patients with multiple past calcium stones, most of whom were receiving increased fluid intake, moderate-strength evidence showed that thiazides (RR, 0.52 [CI, 0.39 to 0.69]), citrates (RR, 0.25 [CI, 0.14 to 0.44]), and allopurinol (RR, 0.59 [CI, 0.42 to 0.84]) each further reduced composite stone recurrence risk compared with placebo or control, although the benefit from allopurinol seemed limited to patients with baseline hyperuricemia or hyperuricosuria. Other baseline biochemistry measures did not allow prediction of treatment efficacy. Low-strength evidence showed that neither citrate nor allopurinol combined with thiazide was superior to thiazide alone. There were few withdrawals among patients with increased fluid intake, many among those with other dietary interventions and more among those who received thiazide and citrate than among control patients. Reporting of adverse events was poor. Most trial participants had idiopathic calcium stones. Nearly all studies reported a composite (including asymptomatic) stone recurrence outcome. In patients with 1 past calcium stone, increased fluid intake reduced recurrence risk. In patients with multiple past calcium stones, addition of thiazide, citrate, or allopurinol further reduced risk. Agency for Healthcare Research and Quality.
    Annals of internal medicine 04/2013; 158(7):535-43. · 13.98 Impact Factor
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    ABSTRACT: BACKGROUND:: The US Preventive Services Task Force recommended against prostate-specific antigen (PSA) screening for prostate cancer based primarily on 2 large long-term randomized-controlled trials (RCTs) and a systematic review of harms resulting from screening. OBJECTIVE:: To support use of large, long-term randomized trials as the evidence base for clinical guidelines on screening and to draw attention to limitations of modeling studies used for this purpose. METHODS:: We respond to critiques of use of RCTs as the primary evidence base, considering the results of the Prostate, Lung, Colorectal and Ovarian (PLCO) and European Randomized Study of Screening for Prostate Cancer (ERSPC) trials, documented harms resulting from PSA screening, and methodological concerns with modeling studies. RESULTS:: The PLCO and ERSPC provided 11-13 years of follow-up on over 250,000 subjects. The PLCO, despite limitations, is most representative of US populations, screening and treatment practices, and showed no mortality benefit resulting from annual PSA testing after 13 years of follow-up. The confidence interval was narrow and precluded more than a 13% relative mortality reduction. Competing causes of mortality in older men make it progressively less likely that longer follow-up will demonstrate a large absolute reduction in disease-specific mortality. With continued screening, the increasing prevalence of asymptomatic cancers in older men will increase the rate of overdiagnosis. Potential harms from screening and treatment are significant. CONCLUSIONS:: Projections from models are subject to mistaken assumptions and investigator biases, and should not be accorded the same weight as evidence from RCTs. Current empiric evidence is sufficient to support the US Preventive Services Task Force guideline that clinicians should recommend against PSA screening for prostate cancer.
    Medical care 04/2013; 51(4):301-303. · 3.24 Impact Factor
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    ABSTRACT: IMPORTANCE Restless legs syndrome (RLS) is a neurological disorder characterized by unpleasant sensations in the legs and a distressing, irresistible urge to move them. We conducted a systematic review to evaluate efficacy, safety, and comparative effectiveness of pharmacologic treatments for primary RLS. EVIDENCE ACQUISITION We included randomized controlled trials (RCTs), published in English, reporting efficacy outcomes and harms of pharmacologic treatments for primary RLS of at least 4 weeks' duration. MEDLINE and other databases were searched through June 2012. Reviewers extracted outcomes and adverse events and rated the strength of evidence. RESULTS We identified 29 eligible RCTs. We found high-strength evidence that the proportion of patients who had a clinically important response (International Restless Legs Syndrome [IRLS] responders), defined as a 50% or greater reduction from baseline in mean IRLS symptom scale scores, was greater with dopamine agonist therapy compared with placebo (61% vs 41%) (risk ratio, 1.60 [95% CI, 1.38-1.86]; 7 trials). Dopamine agonists also improved patient-reported sleep scale scores and quality-of-life measures. High-strength evidence demonstrated that calcium channel alpha-2-delta ligands increased the proportion of IRLS responders compared with placebo (61% vs 37%) (risk ratio, 1.66 [95% CI, 1.33-2.09]; 3 trials). Adverse events associated with dopamine agonists included nausea, vomiting, and somnolence. Alpha-2-delta ligands adverse events included somnolence and unsteadiness or dizziness. CONCLUSIONS AND RELEVANCE On the basis of short-term RCTs that enrolled highly selected populations with long-term high-moderate to very severe symptoms, dopamine agonists and calcium channel alpha-2-delta ligands reduced RLS symptoms and improved sleep outcomes and disease-specific quality of life. Adverse effects and treatment withdrawals due to adverse effects were common.
    JAMA Internal Medicine 03/2013; · 13.25 Impact Factor
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    ABSTRACT: Excerpt This Future Research Needs (FRN) project is a followup to the draft Comparative Effectiveness Review (CER), “Treatment for Restless Legs Syndrome.” The review was motivated by uncertainty around the effectiveness and comparative effectiveness of treatments for restless legs syndrome (RLS). The purpose of this FRN project is to identify and prioritize specific gaps in the current literature about the effectiveness and comparative effectiveness of treatments for RLS for which additional research would aid decisionmakers. We used a deliberative process to identify evidence gaps, translate gaps into researchable questions, and solicit stakeholder opinion on the importance of research questions. This report proposes specific research needs along with research design considerations that may be useful in advancing the field.
    AHRQ Comparative Effectiveness Reviews. 02/2013;
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    ABSTRACT: OBJECTIVE: To determine effectiveness and comparative effectiveness of multidisciplinary rehabilitation programs for moderate to severe TBI in improving participation-related outcomes in adults. This manuscript presents results of select key questions from a recent Agency for Healthcare Quality and Research (AHRQ) comparative effectiveness review. DATA SOURCES: MEDLINE(®), Cochrane Central Register of Controlled Trials, and PsycINFO; hand searches of previous relevant reviews. STUDY SELECTION: We included prospective controlled studies that evaluated effectiveness or comparative effectiveness of multidisciplinary rehabilitation programs delivered to adults with moderate to severe TBI on their participation in life and community. DATA EXTRACTION: We extracted data, assessed risk of bias, and evaluated strength of evidence. Participation was selected as our primary outcome and included measures of productivity (e.g., return to employment or military service) and select scales measuring community integration. Only studies with a low or moderate risk of bias were synthesized. DATA SYNTHESIS: Twelve studies met our inclusion criteria; of these, 8 were of low or moderate risk of bias (4 randomized controlled trials of 680 patients and 4 cohort studies of 190 patients, sample size 36 to 366). Heterogeneous populations, interventions, and outcomes precluded pooled analysis. Evidence was insufficient to draw conclusions about effectiveness. Evidence on comparative effectiveness often demonstrated that improvements were not different between groups; however, this evidence was low strength and may have limited generalizability. CONCLUSIONS: Our review used a rigorous systematic review methodology and focused on participation after multidisciplinary rehabilitation programs for impairments from moderate to severe TBI. The available evidence did not demonstrate superiority of one approach over another. This conclusion is consistent with previous reviews that examined other patient-centered outcomes. While these findings will have little clinical impact, they do point out the limited evidence available to assess effectiveness and comparative effectiveness while highlighting important issues to consider in future comparative effectiveness research on this topic.
    Archives of physical medicine and rehabilitation 01/2013; · 2.18 Impact Factor

Publication Stats

8k Citations
1,483.20 Total Impact Points

Institutions

  • 2000–2013
    • Massachusetts General Hospital
      • Hospital Medicine Unit
      Boston, Massachusetts, United States
    • Blue Cross and Blue Shield Association, Technology Evaluation Center (TEC)
      Chicago, Illinois, United States
  • 1994–2013
    • University of Minnesota Duluth
      • Medical School
      Duluth, Minnesota, United States
  • 2004–2012
    • University of New Mexico
      • • Division of General Internal Medicine
      • • School of Medicine
      Albuquerque, NM, United States
    • Geisel School of Medicine at Dartmouth
      Hanover, New Hampshire, United States
  • 2000–2012
    • U.S. Department of Veterans Affairs
      • • Center for Chronic Disease Outcomes Research (CCDOR)
      • • Geriatric Research, Education and Clinical Center (GRECC)
      • • General Internal Medicine
      Washington, D. C., DC, United States
  • 1990–2012
    • Minneapolis Veterans Affairs Hospital
      • Department of Veterans Affairs
      Minneapolis, Minnesota, United States
  • 2011
    • University of Michigan
      • Department of Radiology
      Ann Arbor, MI, United States
  • 2007–2011
    • Monash University (Australia)
      • School of Public Health and Preventive Medicine
      Melbourne, Victoria, Australia
    • University of Washington Seattle
      • Department of Urology
      Seattle, WA, United States
  • 2003–2011
    • University of Minnesota Twin Cities
      • • Division of Health Policy and Management
      • • Department of Orthopaedic Surgery
      • • Department of Medicine
      • • School of Public Health
      Minneapolis, MN, United States
    • Northwest Medical Center
      Tucson, Arizona, United States
  • 2000–2011
    • BC Cancer Agency
      Vancouver, British Columbia, Canada
  • 1999–2011
    • VHA National Center for Organization Development (NCOD)
      Cincinnati, Ohio, United States
  • 2009–2010
    • University of California, San Diego
      • Division of Urology
      San Diego, California, United States
    • Cook County Hospital
      Chicago, Illinois, United States
    • University of Ottawa
      Ottawa, Ontario, Canada
    • Ottawa Hospital Research Institute
      • Clinical Epidemiology Program
      Ottawa, Ontario, Canada
  • 2000–2009
    • Velindre NHS Trust
      Cardiff, Wales, United Kingdom
  • 2008
    • Oregon Health and Science University
      Portland, Oregon, United States
  • 2006
    • The University of Hong Kong
      Hong Kong, Hong Kong
    • University of California, Los Angeles
      • Department of Urology
      Los Angeles, CA, United States
    • Edward Hines, Jr. VA Hospital
      Hines, Oregon, United States
  • 2005
    • Hennepin County Medical Center
      Minneapolis, Minnesota, United States
    • Sichuan University
      • Department of Urology
      Chengdu, Sichuan Sheng, China
  • 1995
    • University of Wisconsin, Madison
      • Department of Surgery
      Madison, MS, United States