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Exome and Genome Sequencing and Parallels in Radiology: Searching for Patient-Centered Management of Incidental and Secondary Findings

Kang, Stella K; Spector-Bagdady, Kayte; Caplan, Arthur L; Braithwaite, R Scott
Incidental and secondary findings have become an important by-product of diagnostic testing, and their ramifications affect clinical care, research, and policy. Given parallels in the reporting and management of such findings on diagnostic imaging, radiologists may draw from ongoing discussions in medical genetics to rethink more patient-centered approaches to analogous clinical, ethical, and medicolegal dilemmas. Low-risk incidental findings in particular may be drivers of unnecessary testing, invasive procedures, and overtreatment, with associated financial, psychological, and clinical consequences. As radiologists act in patients' best interests by strengthening standardized guidelines on how each finding merits further diagnostic testing or treatment, perhaps the greatest challenge for producing such guidelines is for low-risk incidental findings, for which adverse consequences are unlikely but associated with substantial uncertainty because of the lack of strong evidence on which to base the recommendations. More uniform recommendations for managing low-risk radiologic incidental findings should therefore aim to provide reasonable options that apply across a spectrum of patient preferences. These will require evaluation through research and will ultimately influence the quality of care. Specific areas for exploration may include (1) better gauging of patient attitudes and preferences regarding low-risk incidental findings, (2) using patient preferences to inform more uniform recommendations for low-risk findings that apply across a spectrum of preferences and help guide shared decision making, and (3) when patients endorse a strong preference not to discover low-risk incidental findings, how it might be possible for professional standards to curtail their generation in specific circumstances.
PMID: 27595197
ISSN: 1558-349x
CID: 2238492

A qualitative study to understand guideline-discordant use of imaging to stage incident prostate cancer

Makarov, Danil V; Sedlander, Erica; Braithwaite, R Scott; Sherman, Scott E; Zeliadt, Steven; Gross, Cary P; Curnyn, Caitlin; Shedlin, Michele
BACKGROUND: Approximately half of veterans with low-risk prostate cancer receive guideline-discordant imaging. Our objective was to identify and describe (1) physician knowledge, attitudes, and practices related to the use of imaging to stage prostate cancer, (2) patient attitudes and behaviors related to use of imaging, and (3) to compare responses across three VA medical centers (VAMCs). METHODS: A qualitative approach was used to explore patient and provider knowledge and behaviors relating to the use of imaging. We conducted 39 semi-structured interviews total-including 22 interviews with patients with newly diagnosed with prostate cancer and 17 interviews with physicians caring for them-between September 2014 and July 2015 at three VAMCs representing a spectrum of inappropriate imaging rates. After core theoretical concepts were identified, the Theoretical Domains Framework (TDF) was selected to explore linkages between themes within the dataset and existing domains within the framework. Interviews were audio-recorded, transcribed verbatim, and then coded and analyzed using Nvivo software. RESULTS: Themes from patient interviews were categorized within four TDF domains. Patients reported little interest in staging as compared to disease treatment (goals), and many could not remember if they had imaging at all (knowledge). Patients tended to trust their doctor to make decisions about appropriate tests (beliefs about capabilities). Some patients expressed a minor concern for radiation exposure, but anxiety about cancer outcomes outweighed these fears (emotion). Themes from physician interviews were categorized within five TDF domains. Most physicians self-reported that they know and trust imaging guidelines (knowledge) yet some were still likely to follow their own intuition, whether due to clinical suspicion or years of experience (beliefs about capabilities). Additionally, physicians reported that medico-legal concerns, fear of missing associated diagnoses (beliefs about consequences), influence from colleagues who image frequently (social influences), and the facility where they practice influences rates of imaging (environmental context). CONCLUSIONS: Interviews with patients and physicians suggest that physicians are the primary (and in some cases only) decision-makers regarding staging imaging for prostate cancer. This finding suggests a physician-targeted intervention may be the most effective strategy to improve guideline-concordant prostate cancer imaging.
PMCID:5010696
PMID: 27590603
ISSN: 1748-5908
CID: 2232672

Tumor Anatomy Scoring and Renal Function for Nephron-Sparing Treatment Selection in Patients With Small Renal Masses: A Microsimulation-Based Decision Analysis

Kang, Stella K; Huang, William C; Skolnik, Edward Y; Gervais, Debra A; Braithwaite, R Scott; Pandharipande, Pari V
OBJECTIVE: The purpose of this article is to compare the effectiveness of a treatment algorithm for small renal tumors incorporating the nephrometry score, a renal tumor anatomy scoring system developed by urologists, with the current standard of uniformly recommended partial nephrectomy in patients with mild-to-moderate chronic kidney disease (CKD). MATERIALS AND METHODS: We developed a state-transition microsimulation model to project life expectancy (LE) in hypothetic patients with baseline mild or moderate CKD undergoing treatment of small renal masses. Our model incorporated the nephrometry score, which is predictive of postsurgical renal function loss. The two tested strategies were uniform treatment with partial nephrectomy and selective treatment based on nephrometry score and CKD stage, including percutaneous ablation for CKD stages 2 or 3a and intermediate-to-high nephrometry score or stage 3b CKD and any nephrometry score; otherwise, partial nephrectomy was assumed for other CKD stages and nephrometry scores. The model accounted for benign and malignant lesions, renal function decline, recurrence, and metastatic disease rates specific to each treatment, mortality by CKD stage, and comorbidities. Sensitivity analysis tested the stability of results when varying key parameters. RESULTS: Selective treatment with partial nephrectomy resulted in an average LE benefit of 0.48 year (95% interpercentile range, 0.42-0.54 year) in 65-year-old men and 0.37 year (95% interpercentile range, 0.30-0.43 year) in 65-year-old women relative to nondiscriminatory surgery, due to worsening CKD and cardiovascular mortality associated with partial nephrectomy. Model results were most sensitive to the rate of renal function decline and CKD-related mortality. CONCLUSION: Nephron-sparing treatment selection for small renal masses based on nephrometry score may improve LE in patients with mild or moderate CKD.
PMID: 27305103
ISSN: 1546-3141
CID: 2145162

Appropriateness of Prostate Cancer Imaging among Veterans in a Delivery System without Incentives for Overutilization

Makarov, Danil V; Hu, Elaine Y C; Walter, Dawn; Braithwaite, R Scott; Sherman, Scott; Gold, Heather T; Zhou, Xiao-Hua Andrew; Gross, Cary P; Zeliadt, Steven B
OBJECTIVE: To determine the frequency of appropriate and inappropriate prostate cancer imaging in an integrated health care system. DATA SOURCES/STUDY SETTING: Veterans Health Administration Central Cancer Registry linked to VA electronic medical records and Medicare claims (2004-2008). STUDY DESIGN: We performed a retrospective cohort study of VA patients diagnosed with prostate cancer (N = 45,084). Imaging (CT, MRI, bone scan, PET) use was assessed among patients with low-risk disease, for whom guidelines recommend against advanced imaging, and among high-risk patients for whom guidelines recommend it. PRINCIPAL FINDINGS: We found high rates of inappropriate imaging among men with low-risk prostate cancer (41 percent) and suboptimal rates of appropriate imaging among men with high-risk disease (70 percent). Veterans utilizing Medicare-reimbursed care had higher rates of inappropriate imaging [OR: 1.09 (1.03-1.16)] but not higher rates of appropriate imaging. Veterans treated in middle [OR: 0.51 (0.47-0.56)] and higher [OR: 0.50 (0.46-0.55)] volume medical centers were less likely to undergo inappropriate imaging without compromising appropriate imaging. CONCLUSIONS: Our results highlight the overutilization of imaging, even in an integrated health care system without financial incentives encouraging provision of health care services. Paradoxically, imaging remains underutilized among high-risk patients who could potentially benefit from it most.
PMCID:4874832
PMID: 26423687
ISSN: 1475-6773
CID: 2114032

Risk of mortality and physiologic injury evident with lower alcohol exposure among HIV infected compared with uninfected men

Justice, Amy C; McGinnis, Kathleen A; Tate, Janet P; Braithwaite, R Scott; Bryant, Kendall J; Cook, Robert L; Edelman, E Jennifer; Fiellin, Lynn E; Freiberg, Matthew S; Gordon, Adam J; Kraemer, Kevin L; Marshall, Brandon D L; Williams, Emily C; Fiellin, David A
BACKGROUND: HIV infected (HIV+) individuals may be more susceptible to alcohol-related harm than uninfected individuals. METHODS: We analyzed data on HIV+ and uninfected individuals in the Veterans Aging Cohort Study (VACS) with an Alcohol Use Disorders Identification Test-Consumption AUDIT-C score from 2008 to 2012. We used Cox proportional hazards models to examine the association between alcohol exposure and mortality through July, 2014; and linear regression models to assess the association between alcohol exposure and physiologic injury based on VACS Index Scores. Models were adjusted for age, race/ethnicity, smoking, and hepatitis C infection. RESULTS: The sample included 18,145 HIV+ and 42,228 uninfected individuals. Among HIV+ individuals, 76% had undetectable HIV-1 RNA (<500copies/ml). The threshold for an association of alcohol use with mortality and physiologic injury differed by HIV status. Among HIV+ individuals, AUDIT-C score >/=4 (hazard ratio [HR] 1.25, 95% CI 1.09-1.44) and >/=30 drinks per month (HR, 1.30, 95% CI 1.14-1.50) were associated with increased risk of mortality. Among uninfected individuals, AUDIT-C score >/=5 (HR, 1.19, 95% CI 1.07-1.32) and >/=70 drinks per month (HR 1.13, 95% CI 1.00-1.28) were associated with increased risk. Similarly, AUDIT-C threshold scores of 5-7 were associated with physiologic injury among HIV+ individuals (beta 0.47, 95% CI 0.22, 0.73) and a score of 8 or more was associated with injury in uninfected (beta 0.29, 95% CI 0.16, 0.42) individuals. CONCLUSIONS: Despite antiretroviral therapy, HIV+ individuals experienced increased mortality and physiologic injury at lower levels of alcohol use compared with uninfected individuals. Alcohol consumption limits should be lower among HIV+ individuals.
PMCID:4792710
PMID: 26861883
ISSN: 1879-0046
CID: 2031202

Number of Drinks to "Feel a Buzz" by HIV Status and Viral Load in Men

McGinnis, Kathleen A; Fiellin, David A; Tate, Janet P; Cook, Robert L; Braithwaite, R Scott; Bryant, Kendall J; Edelman, E Jennifer; Gordon, Adam J; Kraemer, Kevin L; Maisto, Stephen A; Justice, Amy C
The impact of HIV and its treatment on the effects of alcohol remain unclear. Blood alcohol concentrations have been noted to be higher in HIV infected individuals prior to antiretroviral initiation. Our goal was to compare number of drinks to "feel a buzz or high" among HIV infected and uninfected men, stratified by viral load (VL) suppression. Data includes 1478 HIV infected and 1170 uninfected men in the veterans aging cohort study who endorsed current drinking. Mean (SD) number of drinks to feel a buzz was 3.1 (1.7) overall. In multivariable analyses, HIV infected men reported a lower mean number of drinks to feel a buzz compared to uninfected men (coef = -14 for VL < 500; -34 for VL >/= 500; p
PMCID:4780364
PMID: 26936030
ISSN: 1573-3254
CID: 2006382

Is risk stratification ever the same as 'profiling'?

Braithwaite, R Scott; Stevens, Elizabeth R; Caplan, Arthur
Physicians engage in risk stratification as a normative part of their professional duties. Risk stratification has the potential to be beneficial in many ways, and implicit recognition of this potential benefit underlies its acceptance as a cornerstone of the medical profession. However, risk stratification also has the potential to be harmful. We argue that 'profiling' is a term that corresponds to risk stratification strategies in which there is concern that ethical harms exceed likely or proven benefits. In the case of risk stratification for health goals, this would occur most frequently if benefits were obtained by threats to justice, autonomy or privacy. We discuss implications of the potential overlap between risk stratification and profiling for researchers and for clinicians, and we consider whether there are salient characteristics that make a particular risk stratification algorithm more or less likely to overlap with profiling, such as whether the risk stratification algorithm is based on voluntary versus non-voluntary characteristics, based on causal versus non-causal characteristics, or based on signifiers of historical disadvantage. We also discuss the ethical challenges created when a risk stratification scheme helps all subgroups but some more than others, or when risk stratification harms some subgroups but benefits the aggregate group.
PMID: 26796335
ISSN: 1473-4257
CID: 1922222

Are There Scenarios When the Use of Non-Placebo-Control Groups in Experimental Trial Designs Increase Expected Value to Society?

Uyei, Jennifer; Braithwaite, R Scott
BACKGROUND: . Despite the benefits of the placebo-controlled trial design, it is limited by its inability to quantify total benefits and harms. Such trials, for example, are not designed to detect an intervention's placebo or nocebo effects, which if detected could alter the benefit-to-harm balance and change a decision to adopt or reject an intervention. OBJECTIVE: . In this article, we explore scenarios in which alternative experimental trial designs, which differ in the type of control used, influence expected value across a range of pretest assumptions and study sample sizes. METHOD: . We developed a decision model to compare 3 trial designs and their implications for decision making: 2-arm placebo-controlled trial ("placebo-control"), 2-arm intervention v. do nothing trial ("null-control"), and an innovative 3-arm trial design: intervention v. do nothing v. placebo trial ("novel design"). Four scenarios were explored regarding particular attributes of a hypothetical intervention: 1) all benefits and no harm, 2) no biological effect, 3) only biological effects, and 4) surreptitious harm (no biological benefit or nocebo effect). RESULTS: . Scenario 1: When sample sizes were very small, the null-control was preferred, but as sample sizes increased, expected value of all 3 designs converged. Scenario 2: The null-control was preferred regardless of sample size when the ratio of placebo to nocebo effect was >1; otherwise, the placebo-control was preferred. Scenario 3: When sample size was very small, the placebo-control was preferred when benefits outweighed harms, but the novel design was preferred when harms outweighed benefits. Scenario 4: The placebo-control was preferred when harms outweighed placebo benefits; otherwise, preference went to the null-control. LIMITATIONS: . Scenarios are hypothetical, study designs have not been tested in a real-world setting, blinding is not possible in all designs, and some may argue the novel design poses ethical concerns. CONCLUSIONS: . We identified scenarios in which alternative experimental study designs would confer greater expected value than the placebo-controlled trial design. The likelihood and prevalence of such situations warrant further study.
PMID: 25977361
ISSN: 1552-681x
CID: 1878872

Do Alcohol Misuse, Smoking, and Depression Vary Concordantly or Sequentially? A Longitudinal Study of HIV-Infected and Matched Uninfected Veterans in Care

Braithwaite, R Scott; Fang, Yixin; Tate, Janet; Mentor, Sherry M; Bryant, Kendall J; Fiellin, David A; Justice, Amy C
We analyzed temporal patterns of alcohol misuse, smoking, and depression among veterans in care to determine whether these conditions vary concordantly or sequentially. Using the Veterans Aging Cohort Study, harmful alcohol use (AUDIT-C >/= 4), current smoking, and depression (PHQ-9 >/= 8), were measured. In regression analyses, predictors included each outcome condition at baseline, the other two conditions in the same survey, the other two conditions in the immediately preceding survey, number of years since enrollment, and HIV status. We found that current smoking and depression were more common among HIV infected individuals. Harmful alcohol use was more common among uninfected individuals. Temporal analyses suggested a concurrent pattern: each condition was associated with the other two conditions (p < 0.03, OR 1.12-1.66) as well as with the prior presence of the same condition (p < 0.0001; OR 6.38-22.02). Smoking was associated with prior depression after controlling for current depression (OR 1.16; p = 0.003). In conclusion, alcohol misuse, smoking, and depression were temporally concordant and persistent, raising the question of whether they constitute a common syndrome in HIV infected patients and others with chronic diseases.
PMCID:5009622
PMID: 26187007
ISSN: 1573-3254
CID: 1669102

Developing a composite weighted quality metric to reflect the total benefit conferred by a health plan

Taskler, Glen B; Braithwaite, R Scott
OBJECTIVES/OBJECTIVE:To improve individual health quality measures, which are associated with varying degrees of health benefit, and composite quality metrics, which weight individual measures identically. STUDY DESIGN/METHODS:We developed a health-weighted composite quality measure reflecting the total health benefit conferred by a health plan annually, using preventive care as a test case. METHODS:Using national disease prevalence, we simulated a hypothetical insurance panel of individuals aged 25 to 84 years. For each individual, we estimated the gain in life expectancy associated with 1 year of health system exposure to encourage adherence to major preventive care guidelines, controlling for patient characteristics (age, race, gender, comorbidity) and variation in individual adherence rates. This personalized gain in life expectancy was used to proxy for the amount of health benefit conferred by a health plan annually to its members, and formed weights in our health-weighted composite quality measure. We aggregated health benefits across the health insurance membership panel to analyze total health system performance. RESULTS:Our composite quality metric gave the highest weights to health plans that succeeded in implementing tobacco cessation and weight loss. One year of compliance with these goals was associated with 2 to 10 times as much health benefit as compliance with easier-to-follow preventive care services, such as mammography, aspirin, and antihypertensives. For example, for women aged 55 to 64 years, successful interventions to encourage weight loss were associated with 2.1 times the health benefit of blood pressure reduction and 3.9 times the health benefit of increasing adherence with screening mammography. CONCLUSIONS:A single health-weighted quality metric may inform measurement of total health system performance.
PMID: 25880626
ISSN: 1936-2692
CID: 3659482