Publications by authors named "Mark Liebow"

59 Publications

Aspirin and other nonsteroidal anti-inflammatory drugs, statins and risk of non-Hodgkin lymphoma.

Int J Cancer 2021 Aug 8;149(3):535-545. Epub 2021 Mar 8.

Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA.

Non-steroidal anti-inflammatory drugs (NSAIDs) and statin drugs may protect against the development of non-Hodgkin lymphoma (NHL), but data are limited, particularly for NHL subtypes. Furthermore, some in vitro, animal and epidemiologic data suggest there may be a synergistic effect of these two agents, but there has been no test of this hypothesis in NHL. We evaluated the self-reported use of NSAIDs and statins in a clinic-based study of 1703 NHL patients and 2199 frequency-matched controls. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for potential confounding variables. We observed an inverse association of regular use of low-dose aspirin with risk of NHL (OR = 0.82; 95% CI 0.70-0.96) that was stronger with longer duration of use (P < .01). There were no associations for use of regular or extra-strength aspirin, ibuprofen, other NSAIDs, statins or other cholesterol-lowering drugs with NHL risk, while an inverse association with COX-2 inhibitors was equivocal. There was also no interaction of low-dose aspirin and statins on NHL risk. Inverse associations of similar magnitude to all NHL were observed for regular use of low-dose aspirin with diffuse large B-cell, follicular, marginal zone and all other lymphomas, although not all associations were statistically significant. In conclusion, low-dose aspirin but not regular/extra strength aspirin, other NSAIDs or statin use was associated with lower risk of NHL. Beyond the potential for the primary prevention of NHL, these data also point to a role of anti-platelet or other effects of low-dose aspirin in lymphomagenesis that warrant follow-up.
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http://dx.doi.org/10.1002/ijc.33541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192479PMC
August 2021

Perioperative Evaluation and Management of Endocrine Disorders.

Mayo Clin Proc 2020 12 6;95(12):2760-2774. Epub 2020 Nov 6.

Division of General Internal Medicine, Mayo Clinic, Rochester, MN.

Evaluation of endocrine issues is a sometimes overlooked yet important component of the preoperative medical evaluation. Patients with diabetes, thyroid disease, and hypothalamic-pituitary-adrenal axis suppression are commonly encountered in the surgical setting and require unique consideration to optimize perioperative risk. For patients with diabetes, perioperative glycemic control has the strongest association with postsurgical outcomes. The preoperative evaluation should include recommendations for adjustment of insulin and noninsulin diabetic medications before surgery. Recommendations differ based on the type of diabetes, the type of insulin, and the patient's predisposition to hyperglycemia or hypoglycemia. Generally, patients with thyroid dysfunction can safely undergo operations unless they have untreated hyperthyroidism or severe hypothyroidism. Patients with known primary or secondary adrenal insufficiency require supplemental glucocorticoids to prevent adrenal crisis in the perioperative setting. Evidence supporting the use of high-dose supplemental corticosteroids for patients undergoing long-term glucocorticoid therapy is sparse. We discuss an approach to these patients based on the dose and duration of ongoing or recent corticosteroid therapy. As with other components of the preoperative medical evaluation, the primary objective is identification and assessment of the severity of endocrine issues before surgery so that the surgeons, anesthesiologists, and internal medicine professionals can optimize management accordingly.
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http://dx.doi.org/10.1016/j.mayocp.2020.05.004DOI Listing
December 2020

Responsibilities, Strategies, and Practice Factors in Clinical Cost Conversations: a US Physician Survey.

J Gen Intern Med 2020 07 12;35(7):1971-1978. Epub 2020 May 12.

Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN, USA.

Background: Physicians play a key role in mitigating and managing costs in healthcare which are rising.

Objective: Conduct a cross-sectional survey in 2017, comparing results to a 2012 survey to understand US physicians' evolving attitudes and strategies concerning healthcare costs.

Participants: Random sample of 1200 US physicians from the AMA Masterfile.

Measures: Physician views on responsibility for costs of care, enthusiasm for cost-saving strategies, cost-consciousness scale, and practice strategies on addressing cost.

Key Results: Among 1200 physicians surveyed in 2017, 489 responded (41%). In 2017, slightly more physicians reported that physicians have a major responsibility for addressing healthcare costs (32% vs. 27%, p = 0.03). In 2017, more physicians attributed "major responsibility" for addressing healthcare costs to pharmaceutical companies (68% vs. 56%, p < 0.001) and hospital and health systems (63% vs. 56%%, p = 0.008) in contrast to 2012. Fewer respondents in 2017 attributed major responsibility for addressing costs to trial lawyers (53% vs. 59%, p = 0.007) and patients (42% vs. 52%, p < 0.0001) as compared to 2012. Physician enthusiasm for patient-focused cost-containment strategies like high deductible health plans and higher co-pays (62% vs. 42%, p < 0.0001 and 62% vs. 39%, p < 0.0001, not enthusiastic, respectively) declined. Physicians reported that when they discussed cost, it resulted in a change in disease management 56% of the time. Cost-consciousness within surveyed physicians had not changed meaningfully in 2017 since 2012 (31.7 vs. 31.2). Most physicians continued to agree that decision support tools showing costs would be helpful in their practice (> 70%). After adjusting for specialty, political affiliation, practice setting, age, and gender, only democratic/independent affiliation remained a significant predictor of cost-consciousness.

Conclusions And Relevance: US physicians increasingly attribute responsibility for rising healthcare costs to organizations and express less enthusiasm for strategies that increase patient out-of-pocket cost. Interventions that focus on physician knowledge and communication strategies regarding cost of care may be helpful.
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http://dx.doi.org/10.1007/s11606-020-05807-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351917PMC
July 2020

Teaching Social Determinants of Health: A Route to Nudging Practical Change.

Acad Med 2020 03;95(3):329

Research associate, Division of Pulmonary and Critical Care Medicine, Mayo Clinic Rochester, Rochester, Minnesota; ORCID: https://orcid.org/0000-0001-9267-1298. Consultant emeritus, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota.

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http://dx.doi.org/10.1097/ACM.0000000000003105DOI Listing
March 2020

Genetically Determined Height and Risk of Non-hodgkin Lymphoma.

Front Oncol 2019 28;9:1539. Epub 2020 Jan 28.

Interdisciplinary Department of Medicine, University of Bari, Bari, Italy.

Although the evidence is not consistent, epidemiologic studies have suggested that taller adult height may be associated with an increased risk of some non-Hodgkin lymphoma (NHL) subtypes. Height is largely determined by genetic factors, but how these genetic factors may contribute to NHL risk is unknown. We investigated the relationship between genetic determinants of height and NHL risk using data from eight genome-wide association studies (GWAS) comprising 10,629 NHL cases, including 3,857 diffuse large B-cell lymphoma (DLBCL), 2,847 follicular lymphoma (FL), 3,100 chronic lymphocytic leukemia (CLL), and 825 marginal zone lymphoma (MZL) cases, and 9,505 controls of European ancestry. We evaluated genetically predicted height by constructing polygenic risk scores using 833 height-associated SNPs. We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for association between genetically determined height and the risk of four NHL subtypes in each GWAS and then used fixed-effect meta-analysis to combine subtype results across studies. We found suggestive evidence between taller genetically determined height and increased CLL risk (OR = 1.08, 95% CI = 1.00-1.17, = 0.049), which was slightly stronger among women (OR = 1.15, 95% CI: 1.01-1.31, = 0.036). No significant associations were observed with DLBCL, FL, or MZL. Our findings suggest that there may be some shared genetic factors between CLL and height, but other endogenous or environmental factors may underlie reported epidemiologic height associations with other subtypes.
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http://dx.doi.org/10.3389/fonc.2019.01539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6999122PMC
January 2020

Human Pegivirus Infection and Lymphoma Risk: A Systematic Review and Meta-analysis.

Clin Infect Dis 2020 08;71(5):1221-1228

Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA.

Background: Human pegivirus (HPgV) is a single-strand RNA virus belonging to the Flaviviridae. Although no definitive association between HPgV infection and disease has been identified, previous studies have suggested an association of HPgV viremia with risk of lymphomas.

Methods: We conducted a systematic review and meta-analysis, including 1 cohort study and 14 case-control studies, assessing the association of HPgV viremia with adult lymphomas. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random-effects model, overall and by geographic region and lymphoma subtype.

Results: The overall OR for lymphoma was 2.85 (95% CI, 1.98-4.11), with statistically significantly elevated ORs observed in 8 of 15 studies. There was a small amount of heterogeneity among studies (I2 = 28.9%; Q = 18.27, P = .16), and the funnel plot provided no evidence for publication bias. The strongest association with lymphoma risk was observed for studies from Southern Europe (OR, 5.68 [95% CI, 1.98-16.3]), whereas weaker ORs (with 95% CIs) were observed for studies from North America (2.24 [1.76-2.85]), Northern Europe (2.90 [.45-18.7), and the Middle East (2.51 [.87-7.27]), but all of similar magnitude. Participants with HPgV viremia had statistically significantly increased risks (OR [95% CI]) for developing diffuse large B-cell (3.29 [1.63-6.62]), follicular (3.01 [1.95-4.63]), marginal zone (1.90 [1.13-3.18]), and T-cell (2.11 [1.17-3.89]) lymphomas, while the risk for Hodgkin lymphoma (3.53 [.48-25.9]) and chronic lymphocytic leukemia (1.45 [.45-4.66]) were increased but did not achieve statistical significance.

Conclusions: This meta-analysis supports a positive association of HPgV viremia with lymphoma risk, overall and for the major lymphoma subtypes.
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http://dx.doi.org/10.1093/cid/ciz940DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7442854PMC
August 2020

US Physicians' Reactions To ACA Implementation, 2012-17.

Health Aff (Millwood) 2019 09;38(9):1530-1536

Jon Tilburt ( ) is a consultant in the Division of General Internal Medicine and the Division of Health Care Policy and Research, Mayo Clinic Minnesota.

Physicians play a key role in implementing health policy, and US physicians were split in their opinions about the Affordable Care Act (ACA) soon after its implementation began. We readministered elements of a prior survey of US physicians to a similar sample to understand how US physicians' opinions of the ACA may have changed over a crucial five-year implementation period (2012-17), and we compared responses across both surveys. Of the 1,200 physicians to whom we sent a survey in the summer of 2017, 489 responded (a response rate of 41 percent). A majority of respondents (60 percent) believed that the ACA had improved access to care and insurance, yet many (43 percent) felt that it had reduced the affordability of coverage. More physicians agreed in 2017 than in 2012 that the ACA "would turn United States health care in the right direction" (53 percent versus 42 percent), despite reporting perceived worsening in several practice conditions over the same time period. After we adjusted for specialty, political party affiliation, practice setting type, perceived social responsibility, age, and sex, we found that only political party affiliation was a significant predictor of support for the ACA in the 2017 results.
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http://dx.doi.org/10.1377/hlthaff.2019.00224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6764098PMC
September 2019

Genetic overlap between autoimmune diseases and non-Hodgkin lymphoma subtypes.

Genet Epidemiol 2019 10 13;43(7):844-863. Epub 2019 Aug 13.

Medicina Traslazionale, Università del Piemonte Orientale, Vercelli, Italy.

Epidemiologic studies show an increased risk of non-Hodgkin lymphoma (NHL) in patients with autoimmune disease (AD), due to a combination of shared environmental factors and/or genetic factors, or a causative cascade: chronic inflammation/antigen-stimulation in one disease leads to another. Here we assess shared genetic risk in genome-wide-association-studies (GWAS). Secondary analysis of GWAS of NHL subtypes (chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, and marginal zone lymphoma) and ADs (rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis). Shared genetic risk was assessed by (a) description of regional genetic of overlap, (b) polygenic risk score (PRS), (c)"diseasome", (d)meta-analysis. Descriptive analysis revealed few shared genetic factors between each AD and each NHL subtype. The PRS of ADs were not increased in NHL patients (nor vice versa). In the diseasome, NHLs shared more genetic etiology with ADs than solid cancers (p = .0041). A meta-analysis (combing AD with NHL) implicated genes of apoptosis and telomere length. This GWAS-based analysis four NHL subtypes and three ADs revealed few weakly-associated shared loci, explaining little total risk. This suggests common genetic variation, as assessed by GWAS in these sample sizes, may not be the primary explanation for the link between these ADs and NHLs.
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http://dx.doi.org/10.1002/gepi.22242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6763347PMC
October 2019

When Generosity Harms Health Care and Public Health.

Am J Public Health 2019 07;109(7):997-998

Amelia Barwise is with the Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN. Mark Liebow is with the Division of General Internal Medicine, Department of Internal Medicine, Mayo Clinic.

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http://dx.doi.org/10.2105/AJPH.2019.305073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6603488PMC
July 2019

Science of Health Care Delivery: An Innovation in Undergraduate Medical Education to Meet Society's Needs.

Mayo Clin Proc Innov Qual Outcomes 2017 Sep 2;1(2):117-129. Epub 2017 Aug 2.

Department of Radiology, Mayo Clinic, Scottsdale, AZ.

The purpose of this special article is to describe a new, 4-year Science of Health Care Delivery curriculum at Mayo Clinic School of Medicine, including curricular content and structure, methods for instruction, partnership with Arizona State University, and implementation challenges. This curriculum is intended to ensure that graduating medical students enter residency prepared to train and eventually practice within person-centered, community- and population-oriented, science-driven, collaborative care teams delivering high-value care. A Science of Health Care Delivery curriculum in undergraduate medical education is necessary to successfully prepare physicians so as to ensure the best clinical outcomes and patient experience of care, at the lowest cost.
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http://dx.doi.org/10.1016/j.mayocpiqo.2017.07.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6135021PMC
September 2017

History of autoimmune conditions and lymphoma prognosis.

Blood Cancer J 2018 08 1;8(8):73. Epub 2018 Aug 1.

Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.

Autoimmune conditions are strong risk factors for developing lymphoma, but their role in lymphoma prognosis is less clear. In a prospective cohort study, we evaluated self-reported history of eight autoimmune conditions with outcomes in 736 diffuse large B-cell, 703 follicular, 302 marginal zone (MZL), 193 mantle cell (MCL), 297 Hodgkin lymphoma (HL), and 186 T-cell lymphomas. We calculated event-free survival (EFS) and overall survival (OS), and estimated hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for sex, prognostic score, and treatment. History of any of the eight autoimmune conditions ranged from 7.4% in HL to 18.2% in MZL, and was not associated with EFS or OS for any lymphoma subtype. However, there was a positive association of autoimmune conditions primarily mediated by B-cell responses with inferior EFS in MCL (HR = 2.23, CI: 1.15-4.34) and HL (HR = 2.63, CI: 1.04-6.63), which was largely driven by rheumatoid arthritis. Autoimmune conditions primarily mediated by T-cell responses were not found to be associated with EFS or OS in any lymphoma subtype, although there were few events for this exposure. Our results indicate that distinguishing autoimmune conditions primarily mediated by B-cell/T-cell responses may yield insight regarding the impact of this comorbid disease, affecting ~10% of lymphoma patients, on survival.
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http://dx.doi.org/10.1038/s41408-018-0105-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6070501PMC
August 2018

Human Pegivirus infection and lymphoma risk and prognosis: a North American study.

Br J Haematol 2018 09 29;182(5):644-653. Epub 2018 May 29.

Department of Internal Medicine, University of Iowa and Iowa City Veterans Affairs Medical Center, Iowa City, IA, USA.

We evaluated the association of Human Pegivirus (HPgV) viraemia with risk of developing lymphoma, overall and by major subtypes. Because this virus has also been associated with better prognosis in the setting of co-infection with human immunodeficiency virus, we further assessed the association of HPgV with prognosis. We used risk factor data and banked plasma samples from 2094 lymphoma cases newly diagnosed between 2002 and 2009 and 1572 frequency-matched controls. Plasma samples were tested for HPgV RNA by reverse transcription polymerase chain reaction (RT-PCR), and those with RNA concentrations <5000 genome equivalents/ml were confirmed using nested RT-PCR methods. To assess the role of HPgV in lymphoma prognosis, we used 2948 cases from a cohort study of newly diagnosed lymphoma patients (included all cases from the case-control study). There was a positive association of HPgV viraemia with risk of lymphoma overall (Odds ratio = 2·14; 95% confidence interval [CI] 1·63-2·80; P < 0·0001), and for all major subtypes except Hodgkin lymphoma and chronic lymphocytic leukaemia/small lymphocytic lymphoma, and this was not confounded by other lymphoma risk factors. In contrast, there was no association of HPgV viraemia with event-free survival (Hazard ratio [HR] = 1·00; 95% CI 0·85-1·18) or overall survival (HR = 0·97; 95% CI 0·79-1·20) for lymphoma overall, or any of the subtypes. These data support the hypothesis for a role of HPgV in the aetiology of multiple lymphoma subtypes.
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http://dx.doi.org/10.1111/bjh.15416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6108902PMC
September 2018

Association of polygenic risk score with the risk of chronic lymphocytic leukemia and monoclonal B-cell lymphocytosis.

Blood 2018 06 19;131(23):2541-2551. Epub 2018 Apr 19.

Huntsman Cancer Institute and Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT.

Inherited loci have been found to be associated with risk of chronic lymphocytic leukemia (CLL). A combined polygenic risk score (PRS) of representative single nucleotide polymorphisms (SNPs) from these loci may improve risk prediction over individual SNPs. Herein, we evaluated the association of a PRS with CLL risk and its precursor, monoclonal B-cell lymphocytosis (MBL). We assessed its validity and discriminative ability in an independent sample and evaluated effect modification and confounding by family history (FH) of hematological cancers. For discovery, we pooled genotype data on 41 representative SNPs from 1499 CLL and 2459 controls from the InterLymph Consortium. For validation, we used data from 1267 controls from Mayo Clinic and 201 CLL, 95 MBL, and 144 controls with a FH of CLL from the Genetic Epidemiology of CLL Consortium. We used odds ratios (ORs) to estimate disease associations with PRS and c-statistics to assess discriminatory accuracy. In InterLymph, the continuous PRS was strongly associated with CLL risk (OR, 2.49; = 4.4 × 10). We replicated these findings in the Genetic Epidemiology of CLL Consortium and Mayo controls (OR, 3.02; = 7.8 × 10) and observed high discrimination (c-statistic = 0.78). When jointly modeled with FH, PRS retained its significance, along with FH status. Finally, we found a highly significant association of the continuous PRS with MBL risk (OR, 2.81; = 9.8 × 10). In conclusion, our validated PRS was strongly associated with CLL risk, adding information beyond FH. The PRS provides a means of identifying those individuals at greater risk for CLL as well as those at increased risk of MBL, a condition that has potential clinical impact beyond CLL.
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http://dx.doi.org/10.1182/blood-2017-11-814608DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5992865PMC
June 2018

Lupus-related single nucleotide polymorphisms and risk of diffuse large B-cell lymphoma.

Lupus Sci Med 2017 12;4(1):e000187. Epub 2017 Nov 12.

Department of Health Sciences, University of York, York, UK.

Objective: Determinants of the increased risk of diffuse large B-cell lymphoma (DLBCL) in SLE are unclear. Using data from a recent lymphoma genome-wide association study (GWAS), we assessed whether certain lupus-related single nucleotide polymorphisms (SNPs) were also associated with DLBCL.

Methods: GWAS data on European Caucasians from the International Lymphoma Epidemiology Consortium (InterLymph) provided a total of 3857 DLBCL cases and 7666 general-population controls. Data were pooled in a random-effects meta-analysis.

Results: Among the 28 SLE-related SNPs investigated, the two most convincingly associated with risk of DLBCL included the CD40 SLE risk allele rs4810485 on chromosome 20q13 (OR per risk allele=1.09, 95% CI 1.02 to 1.16, p=0.0134), and the HLA SLE risk allele rs1270942 on chromosome 6p21.33 (OR per risk allele=1.17, 95% CI 1.01 to 1.36, p=0.0362). Of additional possible interest were rs2205960 and rs12537284. The rs2205960 SNP, related to a cytokine of the tumour necrosis factor superfamily TNFSF4, was associated with an OR per risk allele of 1.07, 95% CI 1.00 to 1.16, p=0.0549. The OR for the rs12537284 (chromosome 7q32, IRF5 gene) risk allele was 1.08, 95% CI 0.99 to 1.18, p=0.0765.

Conclusions: These data suggest several plausible genetic links between DLBCL and SLE.
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http://dx.doi.org/10.1136/lupus-2016-000187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5715504PMC
November 2017

Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia.

Nat Commun 2017 02 6;8:14175. Epub 2017 Feb 6.

Department of Haematology, Royal Victoria Infirmary, Newcastle upon Tyne NE1 4LP, UK.

Several chronic lymphocytic leukaemia (CLL) susceptibility loci have been reported; however, much of the heritable risk remains unidentified. Here we perform a meta-analysis of six genome-wide association studies, imputed using a merged reference panel of 1,000 Genomes and UK10K data, totalling 6,200 cases and 17,598 controls after replication. We identify nine risk loci at 1p36.11 (rs34676223, P=5.04 × 10), 1q42.13 (rs41271473, P=1.06 × 10), 4q24 (rs71597109, P=1.37 × 10), 4q35.1 (rs57214277, P=3.69 × 10), 6p21.31 (rs3800461, P=1.97 × 10), 11q23.2 (rs61904987, P=2.64 × 10), 18q21.1 (rs1036935, P=3.27 × 10), 19p13.3 (rs7254272, P=4.67 × 10) and 22q13.33 (rs140522, P=2.70 × 10). These new and established risk loci map to areas of active chromatin and show an over-representation of transcription factor binding for the key determinants of B-cell development and immune response.
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http://dx.doi.org/10.1038/ncomms14175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5303820PMC
February 2017

Genetically predicted longer telomere length is associated with increased risk of B-cell lymphoma subtypes.

Hum Mol Genet 2016 Apr 9;25(8):1663-76. Epub 2016 Feb 9.

Centre for Big Data Research in Health, University of New South Wales, Sydney, NSW, Australia.

Evidence from a small number of studies suggests that longer telomere length measured in peripheral leukocytes is associated with an increased risk of non-Hodgkin lymphoma (NHL). However, these studies may be biased by reverse causation, confounded by unmeasured environmental exposures and might miss time points for which prospective telomere measurement would best reveal a relationship between telomere length and NHL risk. We performed an analysis of genetically inferred telomere length and NHL risk in a study of 10 102 NHL cases of the four most common B-cell histologic types and 9562 controls using a genetic risk score (GRS) comprising nine telomere length-associated single-nucleotide polymorphisms. This approach uses existing genotype data and estimates telomere length by weighing the number of telomere length-associated variant alleles an individual carries with the published change in kb of telomere length. The analysis of the telomere length GRS resulted in an association between longer telomere length and increased NHL risk [four B-cell histologic types combined; odds ratio (OR) = 1.49, 95% CI 1.22-1.82,P-value = 8.5 × 10(-5)]. Subtype-specific analyses indicated that chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) was the principal NHL subtype contributing to this association (OR = 2.60, 95% CI 1.93-3.51,P-value = 4.0 × 10(-10)). Significant interactions were observed across strata of sex for CLL/SLL and marginal zone lymphoma subtypes as well as age for the follicular lymphoma subtype. Our results indicate that a genetic background that favors longer telomere length may increase NHL risk, particularly risk of CLL/SLL, and are consistent with earlier studies relating longer telomere length with increased NHL risk.
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http://dx.doi.org/10.1093/hmg/ddw027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4854019PMC
April 2016

Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia.

Nat Commun 2016 Mar 9;7:10933. Epub 2016 Mar 9.

Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Gaithersburg, Maryland 20877, USA.

Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and 7,667 controls with follow-up replication in 1,958 cases and 5,530 controls. Here we report three new loci at 3p24.1 (rs9880772, EOMES, P=2.55 × 10(-11)), 6p25.2 (rs73718779, SERPINB6, P=1.97 × 10(-8)) and 3q28 (rs9815073, LPP, P=3.62 × 10(-8)), as well as a new independent SNP at the known 2q13 locus (rs9308731, BCL2L11, P=1.00 × 10(-11)) in the combined analysis. We find suggestive evidence (P<5 × 10(-7)) for two additional new loci at 4q24 (rs10028805, BANK1, P=7.19 × 10(-8)) and 3p22.2 (rs1274963, CSRNP1, P=2.12 × 10(-7)). Pathway analyses of new and known CLL loci consistently show a strong role for apoptosis, providing further evidence for the importance of this biological pathway in CLL susceptibility.
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http://dx.doi.org/10.1038/ncomms10933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4786871PMC
March 2016

Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for Thirteen Cancer Types.

J Natl Cancer Inst 2015 Dec 12;107(12):djv279. Epub 2015 Oct 12.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD (JNS, OP, SIB, QL, CCA, LTA, JDF, MTL, LM, SAS, PRT, KAM, PR, DA, DB, BAB, AB, LBr, WHC, CCC, JSC, JFFJr, NDF, LEBF, MGC, AMG, RNH, NH, WH, PDI, BTJ, CK, CMK, LML, MSL, LEM, LPO, RSSS, WeiT, MT, CWa, SW, NW, KY, PH, LMM, NEC, NR, DTS, SJC, NC); Information Management Services, Silver Spring, MD (WAW, CG); Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Gaithersburg, MD (MY, ZW, LBu, AH, CLi); Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (IDV, KAB, BMB, CoC, MCB, CF, EG, SL, JP, MSt, DJH); Department of Epidemiology, Harvard School of Public Health, Boston, MA (IDV, OA, KAB, CoC, MCB, EG, RSK, SL, JP, HDS, MSt, DTr, DJH, PK); Ontario Health Study, Toronto, Ontario, Canada (MPP); Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden (HOA, EWe); Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden (AA, MF); UCL Cancer Institute, London, UK (MFA, AMF, DH); Royal National Orthopaedic Hospital NHS Trust, Stanmore, Middlesex, UK (MFA, AMF, DH, RT); Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China (SJA, JS, YLW, XCZ); Department of Radiation Sciences, Oncology, Umea University, Umea, Sweden (UA, RH, BSM); Division of Urologic Surgery, Washington University School of Medicine, Saint Louis, MO (GAJr, RGIII); Litwin Centre for Cancer Genetics, University of Toronto, Ontario, Canada (ILA, NG, JSW); Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada (ILA, SG, NG, JSW); Hematology Unit, Ospedale Oncologico di Riferimento Regionale A. Businco, Cagliari, Italy (EA); Department of Medicin

Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites.

Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers.

Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, hl (2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (ρ = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (ρ = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (ρ = 0.51, SE =0.18), and bladder and lung (ρ = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures.

Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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http://dx.doi.org/10.1093/jnci/djv279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4806328PMC
December 2015

Why the C-statistic is not informative to evaluate early warning scores and what metrics to use.

Crit Care 2015 Aug 13;19:285. Epub 2015 Aug 13.

Division of General Internal Medicine, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN, 55905, USA.

Metrics typically used to report the performance of an early warning score (EWS), such as the area under the receiver operator characteristic curve or C-statistic, are not useful for pre-implementation analyses. Because physiological deterioration has an extremely low prevalence of 0.02 per patient-day, these metrics can be misleading. We discuss the statistical reasoning behind this statement and present a novel alternative metric more adequate to operationalize an EWS. We suggest that pre-implementation evaluation of EWSs should include at least two metrics: sensitivity; and either the positive predictive value, number needed to evaluate, or estimated rate of alerts. We also argue the importance of reporting each individual cutoff value.
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http://dx.doi.org/10.1186/s13054-015-0999-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4535737PMC
August 2015

Non-Hodgkin Lymphoma, Body Mass Index, and Cytokine Polymorphisms: A Pooled Analysis from the InterLymph Consortium.

Cancer Epidemiol Biomarkers Prev 2015 Jul 11;24(7):1061-70. Epub 2015 May 11.

Epidemiology and Cancer Statistics Group, Department of Health Sciences, University of York, United Kingdom.

Background: Excess adiposity has been associated with lymphomagenesis, possibly mediated by increased cytokine production causing a chronic inflammatory state. The relationship between obesity, cytokine polymorphisms, and selected mature B-cell neoplasms is reported.

Method: Data on 4,979 cases and 4,752 controls from nine American/European studies from the InterLymph consortium (1988-2008) were pooled. For diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), joint associations of body mass index (from self-reported height and weight) and 12 polymorphisms in cytokines IL1A (rs1800587), IL1B (rs16944, rs1143627), IL1RN (rs454078), IL2 (rs2069762), IL6 (rs1800795, rs1800797), IL10 (rs1800890, rs1800896), TNF (rs1800629), LTA (rs909253), and CARD15 (rs2066847) were investigated using unconditional logistic regression. BMI-polymorphism interaction effects were estimated using the relative excess risk due to interaction (RERI).

Results: Obesity (BMI ≥ 30 kg/m(2)) was associated with DLBCL risk [OR = 1.33; 95% confidence interval (CI), 1.02-1.73], as was TNF-308GA+AA (OR = 1.24; 95% CI, 1.07-1.44). Together, being obese and TNF-308GA+AA increased DLBCL risk almost 2-fold relative to those of normal weight and TNF-308GG (OR = 1.93; 95% CI, 1.27-2.94), with a RERI of 0.41 (95% CI, -0.05-0.84; Pinteraction = 0.13). For FL and CLL/SLL, no associations with obesity or TNF-308GA+AA, either singly or jointly, were observed. No evidence of interactions between obesity and the other polymorphisms were detected.

Conclusions: Our results suggest that cytokine polymorphisms do not generally interact with BMI to increase lymphoma risk but obesity and TNF-308GA+AA may interact to increase DLBCL risk.

Impact: Studies using better measures of adiposity are needed to further investigate the interactions between obesity and TNF-308G>A in the pathogenesis of lymphoma.
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http://dx.doi.org/10.1158/1055-9965.EPI-14-1355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4490950PMC
July 2015

A genome-wide association study of marginal zone lymphoma shows association to the HLA region.

Nat Commun 2015 Jan 8;6:5751. Epub 2015 Jan 8.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA.

Marginal zone lymphoma (MZL) is the third most common subtype of B-cell non-Hodgkin lymphoma. Here we perform a two-stage GWAS of 1,281 MZL cases and 7,127 controls of European ancestry and identify two independent loci near BTNL2 (rs9461741, P=3.95 × 10(-15)) and HLA-B (rs2922994, P=2.43 × 10(-9)) in the HLA region significantly associated with MZL risk. This is the first evidence that genetic variation in the major histocompatibility complex influences MZL susceptibility.
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http://dx.doi.org/10.1038/ncomms6751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4287989PMC
January 2015

Genome-wide association study identifies five susceptibility loci for follicular lymphoma outside the HLA region.

Am J Hum Genet 2014 Oct;95(4):462-71

Epidemiology Research Program, American Cancer Society, Atlanta, GA 30303, USA.

Genome-wide association studies (GWASs) of follicular lymphoma (FL) have previously identified human leukocyte antigen (HLA) gene variants. To identify additional FL susceptibility loci, we conducted a large-scale two-stage GWAS in 4,523 case subjects and 13,344 control subjects of European ancestry. Five non-HLA loci were associated with FL risk: 11q23.3 (rs4938573, p = 5.79 × 10(-20)) near CXCR5; 11q24.3 (rs4937362, p = 6.76 × 10(-11)) near ETS1; 3q28 (rs6444305, p = 1.10 × 10(-10)) in LPP; 18q21.33 (rs17749561, p = 8.28 × 10(-10)) near BCL2; and 8q24.21 (rs13254990, p = 1.06 × 10(-8)) near PVT1. In an analysis of the HLA region, we identified four linked HLA-DRβ1 multiallelic amino acids at positions 11, 13, 28, and 30 that were associated with FL risk (pomnibus = 4.20 × 10(-67) to 2.67 × 10(-70)). Additional independent signals included rs17203612 in HLA class II (odds ratio [OR(per-allele)] = 1.44; p = 4.59 × 10(-16)) and rs3130437 in HLA class I (OR(per-allele) = 1.23; p = 8.23 × 10(-9)). Our findings further expand the number of loci associated with FL and provide evidence that multiple common variants outside the HLA region make a significant contribution to FL risk.
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http://dx.doi.org/10.1016/j.ajhg.2014.09.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4185120PMC
October 2014

Genome-wide association study identifies multiple susceptibility loci for diffuse large B cell lymphoma.

Nat Genet 2014 Nov 28;46(11):1233-8. Epub 2014 Sep 28.

1] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA. [2] Medical Research Council (MRC)-Public Health England (PHE) Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.

Diffuse large B cell lymphoma (DLBCL) is the most common lymphoma subtype and is clinically aggressive. To identify genetic susceptibility loci for DLBCL, we conducted a meta-analysis of 3 new genome-wide association studies (GWAS) and 1 previous scan, totaling 3,857 cases and 7,666 controls of European ancestry, with additional genotyping of 9 promising SNPs in 1,359 cases and 4,557 controls. In our multi-stage analysis, five independent SNPs in four loci achieved genome-wide significance marked by rs116446171 at 6p25.3 (EXOC2; P = 2.33 × 10(-21)), rs2523607 at 6p21.33 (HLA-B; P = 2.40 × 10(-10)), rs79480871 at 2p23.3 (NCOA1; P = 4.23 × 10(-8)) and two independent SNPs, rs13255292 and rs4733601, at 8q24.21 (PVT1; P = 9.98 × 10(-13) and 3.63 × 10(-11), respectively). These data provide substantial new evidence for genetic susceptibility to this B cell malignancy and point to pathways involved in immune recognition and immune function in the pathogenesis of DLBCL.
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http://dx.doi.org/10.1038/ng.3105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4213349PMC
November 2014

Etiologic heterogeneity among non-Hodgkin lymphoma subtypes: the InterLymph Non-Hodgkin Lymphoma Subtypes Project.

J Natl Cancer Inst Monogr 2014 Aug;2014(48):130-44

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD (LMM, SMM, JSC, PH, NR, AB, KPC, QL, SIB, MSL, JNS); Department of Health Sciences Research (SLS, JRC, TMH), Division of Hematology (TGC), and Divison of General Internal Medicine (ML), College of Medicine, Mayo Clinic, Rochester, MN; Department of Cancer Etiology, City of Hope Beckman Research Institute, Duarte, CA (SSW, LB, AL); Prince of Wales Clinical School, University of New South Wales, Sydney, Australia (CMV); Department of Epidemiology, Comprehensive Cancer Center, University of Alabama, Birmingham, AL (CFS); Department of Epidemiology and Biostatistics, School of Medicine, University of California San Francisco, San Francisco, CA (PMB, EAH); Unit of Infections and Cancer (UNIC), Cancer Epidemiology Research Programme, Institut Català d' Oncologia, IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain, CIBER de Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain (SdS, YB); Unit of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden (KES); Department of Health Studies, University of Chicago, Chicago, IL (BCHC); Department of Environmental Health Sciences (YZ, TZ) and Department of Biostatistics (TRH), Yale School of Public Health, New Haven, CT; INSERM, Centre for Research in Epidemiology and Population Health (CESP), U1018, Environmental Epidemiology of Cancer Group, Villejuif, France, Univ Paris Sud, UMRS 1018, Villejuif, France (AM, JC, LO); Registry of Hematological Malignancies in Gironde, Bergonié Institute, 33076 Bordeaux, France (AM); Department of Histopathology, Douglass Hanly Moir Pathology, Macquarie Park, Australia, The Australian School of Advanced Medicine, Macquarie University, Sydney, Australia (JJT); Department of Medical Epidemiology and Biostatistics (H-OA) and Department of Oncology and Pathology (BG), Karolinska Institutet, Stockholm, Swed

Background: Non-Hodgkin lymphoma (NHL) comprises biologically and clinically heterogeneous subtypes. Previously, study size has limited the ability to compare and contrast the risk factor profiles among these heterogeneous subtypes.

Methods: We pooled individual-level data from 17 471 NHL cases and 23 096 controls in 20 case-control studies from the International Lymphoma Epidemiology Consortium (InterLymph). We estimated the associations, measured as odds ratios, between each of 11 NHL subtypes and self-reported medical history, family history of hematologic malignancy, lifestyle factors, and occupation. We then assessed the heterogeneity of associations by evaluating the variability (Q value) of the estimated odds ratios for a given exposure among subtypes. Finally, we organized the subtypes into a hierarchical tree to identify groups that had similar risk factor profiles. Statistical significance of tree partitions was estimated by permutation-based P values (P NODE).

Results: Risks differed statistically significantly among NHL subtypes for medical history factors (autoimmune diseases, hepatitis C virus seropositivity, eczema, and blood transfusion), family history of leukemia and multiple myeloma, alcohol consumption, cigarette smoking, and certain occupations, whereas generally homogeneous risks among subtypes were observed for family history of NHL, recreational sun exposure, hay fever, allergy, and socioeconomic status. Overall, the greatest difference in risk factors occurred between T-cell and B-cell lymphomas (P NODE < 1.0×10(-4)), with increased risks generally restricted to T-cell lymphomas for eczema, T-cell-activating autoimmune diseases, family history of multiple myeloma, and occupation as a painter. We further observed substantial heterogeneity among B-cell lymphomas (P NODE < 1.0×10(-4)). Increased risks for B-cell-activating autoimmune disease and hepatitis C virus seropositivity and decreased risks for alcohol consumption and occupation as a teacher generally were restricted to marginal zone lymphoma, Burkitt/Burkitt-like lymphoma/leukemia, diffuse large B-cell lymphoma, and/or lymphoplasmacytic lymphoma/Waldenström macroglobulinemia.

Conclusions: Using a novel approach to investigate etiologic heterogeneity among NHL subtypes, we identified risk factors that were common among subtypes as well as risk factors that appeared to be distinct among individual or a few subtypes, suggesting both subtype-specific and shared underlying mechanisms. Further research is needed to test putative mechanisms, investigate other risk factors (eg, other infections, environmental exposures, and diet), and evaluate potential joint effects with genetic susceptibility.
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http://dx.doi.org/10.1093/jncimonographs/lgu013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4155467PMC
August 2014

Addressing the nation's physician workforce needs: The Society of General Internal Medicine (SGIM) recommendations on graduate medical education reform.

J Gen Intern Med 2014 Nov 15;29(11):1546-51. Epub 2014 Apr 15.

Section of General Internal Medicine, Department of Medicine, Boston University School of Medicine, 72 East Concord Street, A-208, Boston, MA, USA,

The Graduate Medical Education (GME) system in the United States (US) has garnered worldwide respect, graduating over 25,000 new physicians from over 8,000 residency and fellowship programs annually. GME is the portal of entry to medical practice and licensure in the US, and the pathway through which resident physicians develop the competence to practice independently and further develop their career plans. The number and specialty distribution of available GME positions shapes the overall composition of our national workforce; however, GME is failing to provide appropriate programs that support the delivery of our society's system of healthcare. This paper, prepared by the Health Policy Education Subcommittee of the Society of General Internal Medicine (SGIM) and unanimously endorsed by SGIM's Council, outlines a set of recommendations on how to reform the GME system to best prepare a physician workforce that can provide high quality, high value, population-based, and patient-centered health care, aligned with the dynamic needs of our nation's healthcare delivery system. These recommendations include: accurate workforce needs assessment, broadened GME funding sources, increased transparency of the use of GME dollars, and implementation of incentives to increase the accountability of GME-funded programs for the preparation and specialty selection of their program graduates.
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http://dx.doi.org/10.1007/s11606-014-2847-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4238189PMC
November 2014

Shared decision-making as a cost-containment strategy: US physician reactions from a cross-sectional survey.

BMJ Open 2014 Jan 14;4(1):e004027. Epub 2014 Jan 14.

Division of General Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA.

Objective: To assess US physicians' attitudes towards using shared decision-making (SDM) to achieve cost containment.

Design: Cross-sectional mailed survey.

Setting: US medical practice.

Participants: 3897 physicians were randomly selected from the AMA Physician Masterfile. Of these, 2556 completed the survey.

Main Outcome Measures: Level of enthusiasm for "Promoting better conversations with patients as a means of lowering healthcare costs"; degree of agreement with "Decision support tools that show costs would be helpful in my practice" and agreement with "should promoting SDM be legislated to control overall healthcare costs".

Results: Of 2556 respondents (response rate (RR) 65%), two-thirds (67%) were 'very enthusiastic' about promoting SDM as a means of reducing healthcare costs. Most (70%) agreed decision support tools that show costs would be helpful in their practice, but only 24% agreed with legislating SDM to control costs. Compared with physicians with billing-only compensation, respondents with salary compensation were more likely to strongly agree that decision support tools showing costs would be helpful (OR 1.4; 95% CI 1.1 to 1.7). Primary care physicians (vs surgeons, OR 1.4; 95% CI 1.0 to 1.6) expressed more enthusiasm for SDM being legislated as a means to address healthcare costs.

Conclusions: Most US physicians express enthusiasm about using SDM to help contain costs. They believe decision support tools that show costs would be useful. Few agree that SDM should be legislated as a means to control healthcare costs.
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http://dx.doi.org/10.1136/bmjopen-2013-004027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3902508PMC
January 2014

Specialty, political affiliation, and perceived social responsibility are associated with U.S. physician reactions to health care reform legislation.

J Gen Intern Med 2014 Feb;29(2):399-403

Background: Little is known about how U.S. physicians’ political affiliations, specialties, or sense of social responsibility relate to their reactions to health care reform legislation.

Objective: To assess U.S. physicians’ impressions about the direction of U.S. health care under the Affordable Care Act (ACA), whether that legislation will make reimbursement more or less fair, and examine how those judgments relate to political affiliation and perceived social responsibility.

Design: A cross-sectional, mailed, self-reported survey.

Participants: Simple random sample of 3,897 U.S.physicians.

Main Measures: Views on the ACA in general, reimbursement under the ACA in particular, and perceived social responsibility.

Key Results: Among 2,556 physicians who responded (RR2: 65 %), approximately two out of five (41 %) believed that the ACA will turn U.S. health care in the right direction and make physician reimbursement less fair (44 %). Seventy-two percent of physicians endorsed a general professional obligation to address societal health policy issues, 65 % agreed that every physician is professionally obligated to care for the uninsured or underinsured, and half (55 %) were willing to accept limits on coverage for expensive drugs and procedures for the sake of expanding access to basic health care. In multivariable analyses, liberals and independents were both substantially more likely to endorse the ACA (OR 33.0 [95 % CI, 23.6–46.2]; OR 5.0 [95 % CI, 3.7–6.8], respectively), as were physicians reporting a salary (OR 1.7 [95 % CI, 1.2–2.5])or salary plus bonus (OR 1.4 [95 % CI, 1.1–1.9)compensation type. In the same multivariate models, those who agreed that addressing societal health policy issues are within the scope of their professional obligations (OR 1.5 [95 % CI, 1.0–2.0]), who believe physicians are professionally obligated to care for the uninsured / under-insured (OR 1.7 [95 % CI,1.3–2.4]), and who agreed with limiting coverage for expensive drugs and procedures to expand insurance coverage (OR 2.3 [95 % CI, 1.8–3.0]), were all significantly more likely to endorse the ACA. Surgeons and procedural specialists were less likely to endorse it (OR 0.5 [95 % CI, 0.4–0.7], OR 0.6 [95 %CI, 0.5–0.9], respectively).

Conclusions: Significant subsets of U.S. physicians express concerns about the direction of U.S. health care under recent health care reform legislation. Those opinions appear intertwined with political affiliation,type of medical specialty, as well as perceived social responsibility.
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http://dx.doi.org/10.1007/s11606-013-2718-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3912299PMC
February 2014

The Mayo Clinic Biobank: a building block for individualized medicine.

Mayo Clin Proc 2013 Sep;88(9):952-62

Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.

Objective: To report the design and implementation of the first 3 years of enrollment of the Mayo Clinic Biobank.

Patients And Methods: Preparations for this biobank began with a 4-day Deliberative Community Engagement with local residents to obtain community input into the design and governance of the biobank. Recruitment, which began in April 2009, is ongoing, with a target goal of 50,000. Any Mayo Clinic patient who is 18 years or older, able to consent, and a US resident is eligible to participate. Each participant completes a health history questionnaire, provides a blood sample, and allows access to existing tissue specimens and all data from their Mayo Clinic electronic medical record. A community advisory board provides ongoing advice and guidance on complex decisions.

Results: After 3 years of recruitment, 21,736 individuals have enrolled. Fifty-eight percent (12,498) of participants are female and 95% (20,541) of European ancestry. Median participant age is 62 years. Seventy-four percent (16,171) live in Minnesota, with 42% (9157) from Olmsted County, where the Mayo Clinic in Rochester, Minnesota, is located. The 5 most commonly self-reported conditions are hyperlipidemia (8979, 41%), hypertension (8174, 38%), osteoarthritis (6448, 30%), any cancer (6224, 29%), and gastroesophageal reflux disease (5669, 26%). Among patients with self-reported cancer, the 5 most common types are nonmelanoma skin cancer (2950, 14%), prostate cancer (1107, 12% in men), breast cancer (941, 4%), melanoma (692, 3%), and cervical cancer (240, 2% in women). Fifty-six percent (12,115) of participants have at least 15 years of electronic medical record history. To date, more than 60 projects and more than 69,000 samples have been approved for use.

Conclusion: The Mayo Clinic Biobank has quickly been established as a valuable resource for researchers.
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http://dx.doi.org/10.1016/j.mayocp.2013.06.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4258707PMC
September 2013

Views of US physicians about controlling health care costs.

JAMA 2013 Jul;310(4):380-8

Division of General Internal Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA.

Importance: Physicians' views about health care costs are germane to pending policy reforms.

Objective: To assess physicians' attitudes toward and perceived role in addressing health care costs.

Design, Setting, And Participants: A cross-sectional survey mailed in 2012 to 3897 US physicians randomly selected from the AMA Masterfile.

Main Outcomes And Measures: Enthusiasm for 17 cost-containment strategies and agreement with an 11-measure cost-consciousness scale.

Results: A total of 2556 physicians responded (response rate = 65%). Most believed that trial lawyers (60%), health insurance companies (59%), hospitals and health systems (56%), pharmaceutical and device manufacturers (56%), and patients (52%) have a "major responsibility" for reducing health care costs, whereas only 36% reported that practicing physicians have "major responsibility." Most were "very enthusiastic" for "promoting continuity of care" (75%), "expanding access to quality and safety data" (51%), and "limiting access to expensive treatments with little net benefit" (51%) as a means of reducing health care costs. Few expressed enthusiasm for "eliminating fee-for-service payment models" (7%). Most physicians reported being "aware of the costs of the tests/treatments [they] recommend" (76%), agreed they should adhere to clinical guidelines that discourage the use of marginally beneficial care (79%), and agreed that they "should be solely devoted to individual patients' best interests, even if that is expensive" (78%) and that "doctors need to take a more prominent role in limiting use of unnecessary tests" (89%). Most (85%) disagreed that they "should sometimes deny beneficial but costly services to certain patients because resources should go to other patients that need them more." In multivariable logistic regression models testing associations with enthusiasm for key cost-containment strategies, having a salary plus bonus or salary-only compensation type was independently associated with enthusiasm for "eliminating fee for service" (salary plus bonus: odds ratio [OR], 3.3, 99% CI, 1.8-6.1; salary only: OR, 4.3, 99% CI, 2.2-8.5). In multivariable linear regression models, group or government practice setting (β = 0.87, 95% CI, 0.29 to 1.45, P = .004; and β = 0.99, 95% CI, 0.20 to 1.79, P = .01, respectively) and having a salary plus bonus compensation type (β = 0.82; 95% CI, 0.32 to 1.33; P = .002) were positively associated with cost-consciousness. Finding the "uncertainty involved in patient care disconcerting" was negatively associated with cost-consciousness (β = -1.95; 95% CI, -2.71 to -1.18; P < .001).

Conclusion And Relevance: In this survey about health care cost containment, US physicians reported having some responsibility to address health care costs in their practice and expressed general agreement about several quality initiatives to reduce cost but reported less enthusiasm for cost containment involving changes in payment models.
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http://dx.doi.org/10.1001/jama.2013.8278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5553287PMC
July 2013

Specialty, Political Affiliation, and Perceived Social Responsibility Are Associated with U.S. Physician Reactions to Health Care Reform Legislation.

J Gen Intern Med 2013 Jun 25. Epub 2013 Jun 25.

Department of General Surgery, Mayo Clinic, 200 1st Street SW, Rochester, MN, 55905, USA.

Background: Little is known about how U.S. physicians' political affiliations, specialties, or sense of social responsibility relate to their reactions to health care reform legislation.

Objective: To assess U.S. physicians' impressions about the direction of U.S. health care under the Affordable Care Act (ACA), whether that legislation will make reimbursement more or less fair, and examine how those judgments relate to political affiliation and perceived social responsibility.

Design: A cross-sectional, mailed, self-reported survey.

Participants: Simple random sample of 3,897 U.S. physicians.

Main Measures: Views on the ACA in general, reimbursement under the ACA in particular, and perceived social responsibility.

Key Results: Among 2,556 physicians who responded (RR2: 65 %), approximately two out of five (41 %) believed that the ACA will turn U.S. health care in the right direction and make physician reimbursement less fair (44 %). Seventy-two percent of physicians endorsed a general professional obligation to address societal health policy issues, 65 % agreed that every physician is professionally obligated to care for the uninsured or underinsured, and half (55 %) were willing to accept limits on coverage for expensive drugs and procedures for the sake of expanding access to basic health care. In multivariable analyses, liberals and independents were both substantially more likely to endorse the ACA (OR 33.0 [95 % CI, 23.6-46.2]; OR 5.0 [95 % CI, 3.7-6.8], respectively), as were physicians reporting a salary (OR 1.7 [95 % CI, 1.2-2.5]) or salary plus bonus (OR 1.4 [95 % CI, 1.1-1.9) compensation type. In the same multivariate models, those who agreed that addressing societal health policy issues are within the scope of their professional obligations (OR 1.5 [95 % CI, 1.0-2.0]), who believe physicians are professionally obligated to care for the uninsured / under-insured (OR 1.7 [95 % CI, 1.3-2.4]), and who agreed with limiting coverage for expensive drugs and procedures to expand insurance coverage (OR 2.3 [95 % CI, 1.8-3.0]), were all significantly more likely to endorse the ACA. Surgeons and procedural specialists were less likely to endorse it (OR 0.5 [95 % CI, 0.4-0.7], OR 0.6 [95 % CI, 0.5-0.9], respectively).

Conclusions: Significant subsets of U.S. physicians express concerns about the direction of U.S. health care under recent health care reform legislation. Those opinions appear intertwined with political affiliation, type of medical specialty, as well as perceived social responsibility.
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http://dx.doi.org/10.1007/s11606-013-2523-0DOI Listing
June 2013
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