Needles in a Haystack: Finding Qualitative and Quantitative Collaborators in Academic Medical Centers.

Translational research is a data-driven process that involves transforming scientific laboratory- and clinic-based discoveries into products and activities with real-world impact to improve individual and population health. Successful execution of translational research requires collaboration between clinical and translational science researchers, who have expertise in a wide variety of domains across the field of medicine, and qualitative and quantitative scientists, who have specialized methodologic expertise across diverse methodologic domains. While many institutions are working to build networks of these specialists, a formalized process is needed to help researchers navigate the network to find the best match and to track the navigation process to evaluate an institution's unmet collaborative needs. In 2018, a novel analytic resource navigation process was developed at Duke University to connect potential collaborators, leverage resources, and foster a community of researchers and scientists. This analytic resource navigation process can be readily adopted by other academic medical centers. The process relies on navigators with broad qualitative and quantitative methodologic knowledge, strong communication and leadership skills, and extensive collaborative experience. The essential elements of the analytic resource navigation process are as follows: (1) strong institutional knowledge of methodologic expertise and access to analytic resources, (2) deep understanding of research needs and methodologic expertise, (3) education of researchers on the role of qualitative and quantitative scientists in the research project, and (4) ongoing evaluation of the analytic resource navigation process to inform improvements. Navigators help researchers determine the type of expertise needed, search the institution to find potential collaborators with that expertise, and document the process to evaluate unmet needs. Although the navigation process can create a basis for an effective solution, some challenges remain, such as having resources to train navigators, comprehensively identifying all potential collaborators, and keeping updated information about resources as methodologists join and leave the institution.

A behavioral cancer pain intervention: A randomized noninferiority trial comparing in-person with videoconference delivery.

OBJECTIVE: Behavioral cancer pain interventions are efficacious for improving important pain outcomes; yet, traditional in-person delivery limits patient access. This study compared videoconference-delivered mobile health pain coping skills training (mPCST) to in-person pain coping skills training (PCST-traditional). METHODS: This study was a randomized, noninferiority trial with cancer patients. Participants (N = 178) were randomly assigned to four, 45-minute sessions of mPCST or PCST-traditional. Session content focused on evidence-based cognitive and behavioral pain management skills. Assessments were completed at baseline, posttreatment, and 3-month posttreatment, and included measures of primary intervention outcomes (ie, pain severity and pain interference) and secondary intervention outcomes (ie, physical symptoms, psychological distress, physical well-being, and self-efficacy). The main study aim tested whether mPCST was more accessible (defined as feasibility, acceptability, patient burden, and engagement) than PCST-traditional. The second aim tested whether mPCST was noninferior to PCST-traditional. RESULTS: mPCST demonstrated significantly greater feasibility (ie, attrition, adherence, and time to completion) than PCST-traditional. Both groups reported similar patient burden and engagement as well as a high degree of acceptability. All intervention outcomes demonstrated noninferiority at posttreatment and, with the exception of physical symptoms, 3-month posttreatment. Concerning the primary intervention outcomes, 95% CIs for the mean differences (d) were below the noninferiority margin of 1 for pain severity (posttreatment d = 0.09, 95% CI, -0.63-0.81; 3 months d = -0.43 95% CI, -1.22-0.36) and pain interference (posttreatment d = -0.11, 95% CI, -0.99-0.76; 3 months d = -0.26 95% CI, -1.14-0.62). CONCLUSION: mPCST is highly accessible and noninferior to PCST-traditional.

Patient-reported distress in Hodgkin lymphoma across the survivorship continuum.

PURPOSE: Hodgkin lymphoma (HL) survivors face long-term, elevated risk of treatment-related sequelae, including psychosocial distress associated with poor health outcomes. The magnitude and sources of distress are not well described in the routine care of HL outside of clinical trials. METHODS: We conducted a retrospective cohort study of patients visiting a tertiary-care center for treatment or long-term follow-up of HL. Patient-reported distress was documented using the National Comprehensive Cancer Network Distress Thermometer (DT) and Problem List. Three survivor groups were compared using descriptive methods: on treatment, surviving < 5 years, and surviving ≥ 5 years since diagnosis. RESULTS: A total of 1524 DT were abstracted for 304 patients (106 on treatment, 77 surviving < 5 years, and 121 surviving ≥ 5 years). Distress was low overall (median DT = 1, inter-quartile range 0-4) and was similar across survivor groups. However, actionable distress (score ≥ 4) was reported at 29.5% of clinical encounters. Patients on treatment more frequently reported actionable distress (32.5% of visits) compared with patients surviving < 5 years (20.4%) and ≥ 5 years (28.7%) (P = 0.065). Distress was associated primarily with physical and emotional problems, especially fatigue, worry, and sleep. We did not observe any associations between distress and clinical prognostic factors. CONCLUSIONS: Distress burden is low in HL, but survivorship is marked by periods of actionable distress, largely related to physical symptoms and emotional issues. This burden may be higher when on treatment and is unrelated to disease-related prognostic factors. Survivorship research typically focuses on the post-therapy period, but our results support testing the efficacy of interventions to address distress in HL during active treatment as well.

Patient-Reported Distress in Myelodysplastic Syndromes and Its Association With Clinical Outcomes: A Retrospective Cohort Study.

Background: NCCN defines distress as a multifactorial, unpleasant emotional experience of a psychological nature that may interfere with patients' ability to cope with cancer symptoms and treatment. Patients with myelodysplastic syndromes (MDS) are at risk for distress due to the largely incurable nature of this hematopoietic malignancy and its symptom burden, yet associations with clinical outcomes are unknown. Methods: We retrospectively reviewed patient-reported distress data from adult ambulatory patients with MDS visiting a single, tertiary care medical center from July 2013 to September 2015. Demographic, diagnostic, treatment, and comorbidity information were abstracted from records along with NCCN Distress Thermometer (DT) and Problem List (PL) scores. Survival was analyzed using the Kaplan-Meier method and Cox proportional hazards regression. Results: We abstracted 376 DT scores (median, 1; range, 0-10) from 606 visits and 110 patients (median, 2 DT scores/patient; range, 1-16). NCCN Guidelines suggest that patients with DT scores ≥4 should be evaluated for referral to specialty services to address unmet needs. A total of 54 patients (49%) had at least 1 DT score ≥4 and 20 (18%) had 2 or more DT scores ≥4; 98 patients (89.1%) reported 1,379 problems during 23,613 person-days of follow-up (median, 4 problems/patient/visit; range, 1-23). The 5 most frequently reported problems were fatigue (181 times; 78 patients), pain (95 times; 46 patients), worry (80 times; 45 patients), sleep (78 times; 41 patients), and tingling hands/feet (68 times; 33 patients). After adjustment for risk stratification at diagnosis, a single point increase on the DT was associated with an increased risk of death (hazard ratio, 1.18; 95% CI, 1.01-1.36). Conclusions: Patients with MDS experience a high burden of distress, and patient-reported distress is associated with clinical outcomes. Distress should be further studied as a prognostic variable and a marker of unmet needs in MDS.

Comparing the Palliative Care Needs of Patients With Hematologic and Solid Malignancies.

CONTEXT: Hematologic cancer patients use palliative care services less frequently than their solid tumor counterparts. Prior work suggests that these patients have a sizable symptom burden, but comparisons between hematologic and solid tumor patients near the end of life are limited. OBJECTIVES: To compare unmet symptom needs in a cohort of hematologic and solid tumor patients referred to specialty palliative care services. METHODS: Using a novel data registry of initial palliative care encounters, we performed a cross-sectional analysis of cancer patients receiving care across 17 sites within the Global Palliative Care Quality Alliance. We compared clinically-significant symptoms (rated as four or greater in severity) between hematologic and solid tumor patients and performed multivariate logistic regression analyses examining the relationship between symptom burden and tumor type. RESULTS: We identified 1235 cancer patients, 108 of which had hematologic malignancies. Pain, dyspnea, nausea, and anorexia burden were as high among patients with hematologic as those with solid malignancies. Blood cancer patients had higher rates of clinically-significant tiredness (51% vs. 42%; P = 0.03) than solid tumor patients. Finally, blood cancer patients had greater odds of being tired (odds ratio 2.19; CI 1.22-3.91) and drowsy (odds ratio 1.81; CI 1.07-3.07) than solid tumor patients independent of age, gender, race, and performance status. CONCLUSIONS: Hematologic and solid tumor patients have significant symptom burden at time of referral to palliative care services. Blood cancer patients may have unique concerns warranting targeted attention, including substantial drowsiness and tiredness. Our findings suggest a need to optimize palliative care usage in the hematologic cancer population.

Design and Rationale of the Metastatic Renal Cell Carcinoma (MaRCC) Registry: A Prospective Academic and Community-Based Study of Patients With Metastatic Renal Cell Cancer.

The Metastatic Renal Cell Cancer Registry, a large, nationally representative, prospective registry of patients with metastatic renal cell carcinoma (mRCC), aims to understand real-world treatment patterns and outcomes of patients with mRCC in routine clinical practice across the United States. This observational study is designed to enroll 500 patients with previously untreated mRCC from approximately 60 academic and community treatment sites; as of December 7, 2016, 500 patients have enrolled at 54 sites. Key endpoints include real-world data on reasons for treatment initiation and discontinuation; treatment regimens; disease progression; patient-reported outcomes; and healthcare resource utilization in this patient population.

Anticholinergic Drug Burden in Noncancer Versus Cancer Patients Near the End of Life.

CONTEXT: Anticholinergic drugs can cause several side effects, impairing cognition and quality of life (QOL). Cancer patients are often exposed to increasing cumulative anticholinergic load (ACL) as they approach death, but this burden has not been examined in patients with nonmalignant diseases. OBJECTIVES: To determine ACL and its impact in noncancer versus cancer palliative care patients. METHODS: We performed a secondary analysis of 244 subjects enrolled in a randomized controlled trial. ACL was quantified with the Anticholinergic Drug Scale. We used multivariable regression to calculate the effect of ACL on key outcomes, including drowsiness, fatigue, and QOL. Patients were stratified by diagnosis, and drugs were grouped as symptom management (SM) or disease management (DM). RESULTS: Overall, ACL in cancer and noncancer patients was not significantly different (2.6 vs. 2.4; P = 0.23). SM drugs caused greater anticholinergic exposure than DM drugs in both cancer and noncancer patients (2.3 vs. 0.5, and 1.5 vs. 1.3, respectively; both P < 0.05); however, DM drugs exposed noncancer patients to relatively more ACL than cancer patients (1.2 vs. 0.6, P < 0.0001). ACL was associated with worse fatigue (odds ratio, 1.08; CI, 1.002-1.17) and worse QOL (odds ratio, 0.89; CI, 0.80-0.98). CONCLUSIONS: ACL is associated with worse fatigue and QOL and may not differ significantly between cancer and noncancer patients nearing end of life. SM drugs are more responsible for ACL in cancer and noncancer patients, although DM drugs contribute significantly to ACL in the latter group. We recommend more attention to reducing anticholinergic use in all patients with life-limiting illness.

A Pilot Study of a Mobile Health Pain Coping Skills Training Protocol for Patients With Persistent Cancer Pain.

CONTEXT: Pain coping skills training (PCST) interventions have shown efficacy for reducing pain and providing other benefits in patients with cancer. However, their reach is often limited because of a variety of barriers (e.g., travel, physical burden, cost, time). OBJECTIVES: This study examined the feasibility and acceptability of a brief PCST intervention delivered to patients in their homes using mobile health (mHealth) technology. Pre-to-post intervention changes in pain, physical functioning, physical symptoms, psychological distress, self-efficacy for pain management, and pain catastrophizing also were examined. METHODS: Patients with a diagnosis of breast, lung, prostate, or colorectal cancer who reported persistent pain (N = 25) participated in a four-session intervention delivered using mHealth technology (videoconferencing on a tablet computer). Participants completed measures of pain, physical functioning, physical symptoms, psychological distress, self-efficacy for pain management, and pain catastrophizing. We also assessed patient satisfaction. RESULTS: Participants completed an average of 3.36 (SD = 1.11) of the four intervention sessions for an overall session completion rate of 84%. Participants reported that the program was of excellent quality and met their needs. Significant preintervention to postintervention differences were found in pain, physical symptoms, psychological distress, and pain catastrophizing. CONCLUSION: The use of mHealth technology is a feasible and acceptable option for delivery of PCST for patients with cancer. This delivery mode is likely to dramatically increase intervention access for cancer patients with pain compared to traditional in-person delivery. Preliminary data also suggest that the program is likely to produce pretreatment to post-treatment decreases in pain and other important outcomes.

Safety and benefit of discontinuing statin therapy in the setting of advanced, life-limiting illness: a randomized clinical trial.

IMPORTANCE: For patients with limited prognosis, some medication risks may outweigh the benefits, particularly when benefits take years to accrue; statins are one example. Data are lacking regarding the risks and benefits of discontinuing statin therapy for patients with limited life expectancy. OBJECTIVE: To evaluate the safety, clinical, and cost impact of discontinuing statin medications for patients in the palliative care setting. DESIGN, SETTING, AND PARTICIPANTS: This was a multicenter, parallel-group, unblinded, pragmatic clinical trial. Eligibility included adults with an estimated life expectancy of between 1 month and 1 year, statin therapy for 3 months or more for primary or secondary prevention of cardiovascular disease, recent deterioration in functional status, and no recent active cardiovascular disease. Participants were randomized to either discontinue or continue statin therapy and were monitored monthly for up to 1 year. The study was conducted from June 3, 2011, to May 2, 2013. All analyses were performed using an intent-to-treat approach. INTERVENTIONS: Statin therapy was withdrawn from eligible patients who were randomized to the discontinuation group. Patients in the continuation group continued to receive statins. MAIN OUTCOMES AND MEASURES: Outcomes included death within 60 days (primary outcome), survival, cardiovascular events, performance status, quality of life (QOL), symptoms, number of nonstatin medications, and cost savings. RESULTS: A total of 381 patients were enrolled; 189 of these were randomized to discontinue statins, and 192 were randomized to continue therapy. Mean (SD) age was 74.1 (11.6) years, 22.0% of the participants were cognitively impaired, and 48.8% had cancer. The proportion of participants in the discontinuation vs continuation groups who died within 60 days was not significantly different (23.8% vs 20.3%; 90% CI, -3.5% to 10.5%; P=.36) and did not meet the noninferiority end point. Total QOL was better for the group discontinuing statin therapy (mean McGill QOL score, 7.11 vs 6.85; P=.04). Few participants experienced cardiovascular events (13 in the discontinuation group vs 11 in the continuation group). Mean cost savings were $3.37 per day and $716 per patient. CONCLUSIONS AND RELEVANCE: This pragmatic trial suggests that stopping statin medication therapy is safe and may be associated with benefits including improved QOL, use of fewer nonstatin medications, and a corresponding reduction in medication costs. Thoughtful patient-provider discussions regarding the uncertain benefit and potential decrement in QOL associated with statin continuation in this setting are warranted. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01415934.

Validation and real-world assessment of the Functional Assessment of Anorexia-Cachexia Therapy (FAACT) scale in patients with advanced non-small cell lung cancer and the cancer anorexia-cachexia syndrome (CACS).

PURPOSE: Patients with cancer anorexia-cachexia syndrome (CACS) suffer a significant symptom burden, impaired quality of life (QoL), and shorter survival. Measurement of QoL impairments related to CACS is thereby important both in clinical practice and in research. We aimed to further validate the Functional Assessment of Anorexia-Cachexia Therapy (FAACT) scale in an advanced lung cancer population. METHODS: We tested the performance of the FAACT and its anorexia-cachexia subscale (ACS) within a dataset of patients with advanced non-small cell lung cancer (aNSCLC), using standard statistical methods. We then compared the performance of commonly used QoL measures stratified by CACS status and by patient self-report of appetite and weight loss. RESULTS: The FAACT and its ACS demonstrate internal validity consistent with acceptable published ranges for other QoL scales (Cronbach alpha = 0.9 and 0.79, respectively). Correlation coefficients demonstrate moderate correlations in the expected directions between FAACT and ACS and scales that measure related constructs. Comparing patients with and without CACS, the ACS is more sensitive to change than other QoL instruments (mean score 33.1 vs. 37.2, p = 0.011, ES = 0.58). CONCLUSION: In patients with aNSCLC, the FAACT and its ACS performed well compared with other instruments, further supporting their validity and value in clinical research. FAACT and ACS scores covaried with symptoms and other QoL changes that are typical hallmarks of CACS, lending further support to their use as QoL endpoints in clinical trials among patients with CACS.

Correlation between the international consensus definition of the Cancer Anorexia-Cachexia Syndrome (CACS) and patient-centered outcomes in advanced non-small cell lung cancer.

CONTEXT: The cancer anorexia-cachexia syndrome (CACS) is common in patients with advanced solid tumors and is associated with adverse outcomes including poor quality of life (QOL), impaired functioning, and shortened survival. OBJECTIVES: To apply the recently posed weight-based international consensus CACS definition to a population of patients with advanced non-small cell lung cancer (NSCLC) and explore its impact on patient-reported outcomes. METHODS: Ninety-nine patients participated in up to four study visits over a six-month period. Longitudinal assessments included measures of physical function, QOL, and other clinical variables such as weight and survival. RESULTS: Patients meeting the consensus CACS criteria at Visit 1 had a significantly shorter median survival (239.5 vs. 446 days; hazard ratio, 2.06, P < 0.05). Physical function was worse in the CACS group (mean Karnofsky Performance Status score 68 vs. 77, Eastern Cooperative Oncology Group Performance Status score 1.8 vs. 1.3, P < 0.05 for both), as was QOL (Functional Assessment of Cancer Therapy-General [FACT-G] Lung Cancer subscale of 17.2 vs. 19.9, Anorexia/Cachexia subscale of 31.4 vs. 37.9, P < 0.05 for both). Differences in the FACT-G and the Functional Assessment of Chronic Illness Therapy-Fatigue subscale approached but did not reach statistical significance. Longitudinally, all measures of physical function and QOL worsened regardless of CACS status, but the rate of decline was more rapid in the CACS group. CONCLUSION: The weight-based component of the recently proposed international consensus CACS definition is useful in identifying patients with advanced NSCLC who are likely to have significantly inferior survival and who will develop more precipitous declines in physical function and QOL. This definition may be useful for clinical screening purposes and identify patients with high palliative care needs.

Patient preferences in advanced or recurrent ovarian cancer.

BACKGROUND: The objective of this study was to elucidate relative preferences of women with ovarian cancer for symptoms, treatment-related side effects, and progression-free survival (PFS) relevant to choosing a treatment regimen. METHODS: Women with advanced or recurrent ovarian cancer participated in a survey that included 3 methods to measure patient preferences (ratings, rankings, and a discrete-choice experiment) for 7 attributes: mode of administration, visit frequency, peripheral neuropathy, nausea and vomiting, fatigue, abdominal discomfort, and PFS. Participants were asked to choose between 2 unlabeled treatment scenarios that were characterized using the 7 attributes. Each participant completed 12 choice questions in which attribute levels were assigned according to an experimental design and a fixed-choice question representing 2 chemotherapy regimens for ovarian cancer. RESULTS: In total, 95 women completed the survey. Participants' ratings and rankings revealed greater concern and importance for PFS than for any other attribute (P < .0001 for all). The discrete-choice experiment revealed that the relative odds that a participant would choose a scenario with 18 months, 21 months, and 24 months of PFS versus 15 months of PFS were 1.5 (P = .01), 3.4 (P < .001), and 7.5 (P < .001), respectively. However, participants' choices indicated that they were willing to accept a shorter PFS to avoid severe side effects: 6.7 months to reduce nausea and vomiting from severe to mild, 5.0 months to reduce neuropathy from severe to mild, and 3.7 months to reduce abdominal symptoms from severe to moderate. CONCLUSIONS: PFS is the predominant driver of patient preferences for chemotherapy regimens. However, women in the current study were willing to trade significant PFS time for reductions in treatment-related toxicity.

Analyzing phase III studies in hospice/palliative care. a solution that sits between intention-to-treat and per protocol analyses: the palliative-modified ITT analysis.

Intention-to-treat (ITT) analyses are the standard way to evaluate randomized controlled trials (RCTs) to minimize Type I errors related to differential rates of noncompletion from one study arm. People in palliative care often die sooner than predicted as a direct result of disease progression, some of whom will be participating in RCTs and who will, therefore, withdraw or die after randomization for reasons unrelated to the intervention. This proportion of withdrawals is statistically negligible in other clinical disciplines, but commonplace in hospice/palliative care, creating a systematic bias away from the true effect. ITT analyses in hospice/palliative care that deem all withdrawals to be treatment failures or that impute data from deteriorating participants systematically underestimate the benefits of interventions, reducing the power of these studies. Equally unacceptable would be a per protocol analysis that excludes all withdrawals after randomization as this will underestimate toxicity. A modified analytic approach is needed on a continuum between ITT and per protocol analyses. To address data after randomization where there is a high rate of withdrawals because of death or deterioration, criteria need to include being: 1) prespecified in the original protocol; 2) clinically absolutely the result of disease progression; 3) identified by the blinded Independent Data Monitoring Committee as being unrelated to the intervention(s); and 4) accounted for in the study's CONSORT diagram. Such data should not be included in the analysis of the primary outcome. This article aims to define a better way of balancing Type I and Type II errors in hospice/palliative care RCT analyses using the palliative-modified ITT analysis. Arguably, the palliative-modified ITT analysis should be the primary evaluation of hospice/palliative care Phase III studies but, as a minimum, should routinely be the key sensitivity analysis.

Aerobic and resistance training effects on energy intake: the STRRIDE-AT/RT study.

PURPOSE: Our study characterizes food and energy intake responses to long-term aerobic training (AT) and resistance training (RT) during a controlled 8-month trial. METHODS: In the STRRIDE-AT/RT trial, overweight/obese sedentary dyslipidemic men and women were randomized to AT (n = 39), RT (n = 38), or a combined treatment (AT/RT, n = 40) without any advice to change their food intakes. Quantitative food intake assessments and food frequency questionnaires were collected at baseline (before training) and after 8 months of training (end of training); body mass (BM) and fat-free mass (FFM) were also assessed. RESULTS: In AT and AT/RT, respectively, meaningful decreases in reported energy intake (REI) (-217 and -202 kcal, P < 0.001) and in intakes of fat (-14.9 and -14.9 g, P < 0.001, P = 0.004), protein (-8.3 and -10.7 g, P = 0.002, P < 0.001), and carbohydrate (-28.1 and -14.7 g, P = 0.001, P = 0.030) were found by food frequency questionnaires. REI relative to FFM decreased (P < 0.001 and P = 0.002), as did intakes of fat (-0.2 and -0.3 g, P = 0.003 and P = 0.014) and protein (-0.1 and -0.2 g, P = 0.005 and P < 0.001) in AT and AT/RT and carbohydrate (-0.5 g, P < 0.003) in AT only. For RT, REI by quantitative daily dietary intake decreased (-3.0 kcal.kg(-1) FFM, P = 0.046), as did fat intake (-0.2 g, P = 0.033). BM decreased in AT (-1.3 kg, P = 0.006) and AT/RT (-1.5 kg, P = 0.001) but was unchanged (0.6 kg, P = 0.176) in RT. CONCLUSIONS: Previously sedentary subjects completing 8 months of AT or AT/RT reduced their intakes of calories and macronutrients and BM. In RT, fat intakes and REI (when expressed per FFM) decreased, BM was unchanged, and FFM increased.

Effects of aerobic vs. resistance training on visceral and liver fat stores, liver enzymes, and insulin resistance by HOMA in overweight adults from STRRIDE AT/RT.

While the benefits of exercise are clear, many unresolved issues surround the optimal exercise prescription. Many organizations recommend aerobic training (AT) and resistance training (RT), yet few studies have compared their effects alone or in combination. The purpose of this study, part of Studies Targeting Risk Reduction Interventions Through Defined Exercise-Aerobic Training and/or Resistance Training (STRRIDE/AT/RT), was to compare the effects of AT, RT, and the full combination (AT/RT) on central ectopic fat, liver enzymes, and fasting insulin resistance [homeostatic model assessment (HOMA)]. In a randomized trial, 249 subjects [18-70 yr old, overweight, sedentary, with moderate dyslipidemia (LDL cholesterol 130-190 mg/dl or HDL cholesterol ≤ 40 mg/dl for men or ≤ 45 mg/dl for women)] performed an initial 4-mo run-in period. Of these, 196 finished the run-in and were randomized into one of the following 8-mo exercise-training groups: 1) RT, which comprised 3 days/wk, 8 exercises, 3 sets/exercise, 8-12 repetitions/set, 2) AT, which was equivalent to ∼19.2 km/wk (12 miles/wk) at 75% peak O(2) uptake, and 3) full AT + full RT (AT/RT), with 155 subjects completing the intervention. The primary outcome variables were as follows: visceral and liver fat via CT, plasma liver enzymes, and HOMA. AT led to significant reductions in liver fat, visceral fat, alanine aminotransferase, HOMA, and total and subcutaneous abdominal fat (all P < 0.05). RT resulted in a decrease in subcutaneous abdominal fat (P < 0.05) but did not significantly improve the other variables. AT was more effective than RT at improving visceral fat, liver-to-spleen ratio, and total abdominal fat (all P < 0.05) and trended toward a greater reduction in liver fat score (P < 0.10). The effects of AT/RT were statistically indistinguishable from the effects of AT. These data show that, for overweight and obese individuals who want to reduce measures of visceral fat and fatty liver infiltration and improve HOMA and alanine aminotransferase, a moderate amount of aerobic exercise is the most time-efficient and effective exercise mode.

Exploration of a hypothesized independent association of a common 9p21.3 gene variant and ischemic stroke in patients with and without angiographic coronary artery disease.

BACKGROUND: Single-nucleotide polymorphisms (SNPs) at the chromosome 9p21.3 locus are associated with coronary artery disease (CAD). An association of this genomic region with ischemic stroke independent of its effect on CAD could suggest an additional, stroke-specific pathophysiological relationship. METHODS: Medical record review was used to identify 548 patients without a history of cerebrovascular disease and 232 who had a verified ischemic stroke or transient ischemic attack (TIA) from the Duke CATHGEN biorepository of patients who had a cardiac catheterization. ANCOVA and multivariable logistic regression modeling were performed to determine independent genetic associations between the key chromosome 9p21.3 SNP, rs10757278, and ischemic stroke by comparing allele frequencies between 229 patients with stroke or TIA and an equal number of matched nonstroke controls, adjusting for other risk factors. In a secondary analysis, controls were further divided based on the presence (n = 353) or absence (n = 195) of angiographic CAD. RESULTS: Allele frequencies were similar between patients with and without a history of ischemic stroke in both additive (p = 0.83) and dominant (p = 0.92) models of genetic risk. There was no association between rs10757278 allele frequency and stroke status based on the presence or absence of angiographically demonstrated CAD in nonstroke controls (ANCOVA, p = 0.99). CONCLUSION: These results provide no evidence of a stroke-specific association of the 9p21.3 locus regardless of the presence or absence of angiographic CAD and highlight the need for larger studies to further evaluate this hypothesized relationship.