Faculty Bibliography

Importance/UNASSIGNED:Duration of untreated psychosis (DUP) has been associated with poor outcomes in schizophrenia, but the mechanism responsible for this association is not known. Objectives/UNASSIGNED:To determine whether hippocampal volume loss occurs during the initial 8 weeks of antipsychotic treatment and whether it is associated with DUP, and to examine molecular biomarkers in association with hippocampal volume loss and DUP. Design, Setting, and Participants/UNASSIGNED:A naturalistic longitudinal study with matched healthy controls was conducted at Shanghai Mental Health Center. Between March 5, 2013, and October 8, 2014, 71 medication-naive individuals with nonaffective first-episode psychosis (FEP) and 73 age- and sex-matched healthy controls were recruited. After approximately 8 weeks, 31 participants with FEP and 32 controls were reassessed. Exposures/UNASSIGNED:The participants with FEP were treated according to standard clinical practice with second-generation antipsychotics. Main Outcomes and Measures/UNASSIGNED:Hippocampal volumetric integrity (HVI) (an automated estimate of the parenchymal fraction in a standardized hippocampal volume of interest), DUP, 13 peripheral molecular biomarkers, and 14 single-nucleotide polymorphisms from 12 candidate genes were determined. Results/UNASSIGNED:The full sample consisted of 71 individuals with FEP (39 women and 32 men; mean [SD] age, 25.2 [7.7] years) and 73 healthy controls (40 women and 33 men; mean [SD] age, 23.9 [6.4] years). Baseline median left HVI was lower in the FEP group (n = 57) compared with the controls (n = 54) (0.9275 vs 0.9512; difference in point estimate, -0.020 [95% CI, -0.029 to -0.010]; P = .001). During approximately 8 weeks of antipsychotic treatment, left HVI decreased in 24 participants with FEP at a median annualized rate of -.03791 (-4.1% annualized change from baseline) compared with an increase of 0.00115 (0.13% annualized change from baseline) in 31 controls (difference in point estimate, -0.0424 [95% CI, -0.0707 to -0.0164]; P = .001). The change in left HVI was inversely associated with DUP (r = -0.61; P = .002). Similar results were found for right HVI, although the association between change in right HVI and DUP did not achieve statistical significance (r = -0.35; P = .10). Exploratory analyses restricted to the left HVI revealed an association between left HVI and markers of inflammation, oxidative stress, brain-derived neurotrophic factor, glial injury, and markers reflecting dopaminergic and glutamatergic transmission. Conclusions and Relevance/UNASSIGNED:An association between longer DUP and accelerated hippocampal atrophy during initial treatment suggests that psychosis may have persistent, possibly deleterious, effects on brain structure. Additional studies are needed to replicate these exploratory findings of molecular mechanisms by which untreated psychosis may affect hippocampal volume and to determine whether these effects account for the known association between longer DUP and poor outcome.

OBJECTIVE:To examine the dose-response effects of aerobic exercise on health-related quality of life (HRQoL) among colon cancer survivors. METHODS:of aerobic exercise (high-dose) for 6 months. HRQoL outcomes included the Short Form (SF)-36 physical and mental component summary, Functional Assessment of Cancer Therapy-Colorectal, Pittsburgh Sleep Quality Index, Fear of Cancer Recurrence Inventory, Fatigue Symptom Inventory, and North Central Cancer Treatment Group bowel function questionnaire, assessed at baseline and post intervention. The primary hypothesis was that exercise would improve HRQoL outcomes in a dose-response fashion, such that high-dose aerobic exercise would yield the largest improvements in HRQoL outcomes. RESULTS: = 0.045) in a dose-response fashion. Between-group standardized mean difference effects sizes for the above-described findings were small to moderate in magnitude (0.35-0.75). No dose-response effects were observed for the mental component summary score of the SF-36, the Fear of Cancer Recurrence Inventory, or bowel function. CONCLUSION:, improve multiple HRQoL outcomes among stage I to III colon cancer survivors. These findings provide evidence that aerobic exercise may provide multiple health benefits for colon cancer survivors.

PURPOSE:To examine the effect of an opt-out default recruitment strategy compared to a conventional opt-in strategy on enrollment and adherence to a behavioral intervention for poorly controlled diabetic patients. DESIGN:Randomized controlled trial. SETTING:University of Pennsylvania primary care practices. PARTICIPANTS:Participants of this trial included those with (1) age 18 to 80 years; (2) diabetes diagnosis; and (3) a measured hemoglobin A1c (HbA1c) greater than 8% in the past 12 months. INTERVENTION:We randomized eligible patients into opt-in and opt-out arms prior to enrollment. Those in the opt-out arm received a letter stating that they were enrolled into a diabetes research study with the option to opt out, and those in the opt-in arm received a standard recruitment letter. MEASURES:Main end points include enrollment rate, defined as the proportion of participants who attended the baseline visit, and adherence to daily glycemic monitoring. ANALYSIS:We powered our study to detect a 20% difference in adherence to device usage between arms and account for a 10% attrition rate. RESULTS:Of the 569 eligible participants who received a recruitment letter, 496 were randomized to the opt-in arm and 73 to the opt-out arm. Enrollment rates were 38% in the opt-out arm and 13% in the opt-in arm ( P < .001). CONCLUSIONS:Opt-out defaults, where clinically appropriate, could be a useful approach for increasing the generalizability of low-risk trials testing behavioral interventions in clinical settings.

BACKGROUND: Observational studies suggest that higher volumes of physical activity are associated with a lower risk of disease recurrence among survivors of colon cancer. However, the feasibility and safety of prescribing higher volumes of physical activity to survivors of colon cancer are unknown. Furthermore, the pathways through which exercise may reduce disease recurrence are unknown. PATIENTS AND METHODS: Survivors of stage I to III colon cancer were randomized to usual-care control, 150 minutes per week of aerobic exercise (low-dose), or 300 minutes per week of aerobic exercise (high-dose). Changes in soluble intercellular adhesion molecule-1 and vascular adhesion molecule-1 prognostic biomarkers were examined. RESULTS: From January 2015 to February 2016, 39 patients were enrolled (n = 13 usual-care control; n = 14 low-dose; n = 12 high-dose), and 38 participants completed the study (97% follow-up). Over 6 months, the low-dose group completed 142 minutes per week (92.8% adherence), and the high-dose group completed 247 minutes per week (89.0% adherence) of exercise. Compared with the control group, changes in soluble intercellular adhesion molecule-1 were -134.9 ng/mL (95% confidence interval, -238.1 to -31.6 ng/mL) in the low-dose group and -114.8 ng/mL (95% confidence interval, -222.5 to -7.1 ng/mL) in the high-dose group (linear Ptrend = .023; nonlinear Ptrend = .044). No changes were observed for soluable vascular adhesion molecule-1 (linear Ptrend = .791; nonlinear Ptrend = .604). Non-serious adverse events occurred at similar rates among randomized groups. No serious adverse events occurred. CONCLUSION: Higher volumes of moderate-intensity aerobic exercise, up to 300 minutes per week, are feasible, safe, and elicit favorable changes in prognostic biomarkers among patients recently treated for stage I to III colon cancer. These data can be used to guide clinical recommendations for patients, and inform future trials.

PURPOSE/OBJECTIVE:To determine whether different financial incentives are effective in promoting weight loss among prediabetic Medicaid recipients. DESIGN/METHODS:Four-group, multicenter, randomized clinical trial. SETTING AND PARTICIPANTS/METHODS:Medicaid managed care enrollees residing in New York, aged 18 to 64 years, and diagnosed as prediabetic or high risk for diabetes (N = 703). INTERVENTION/METHODS:In a 16-week program, participants were randomly assigned to one of 4 arms: (1) control (no incentives), (2) process incentives for attending weekly Diabetes Prevention Program sessions, (3) outcome incentives for achieving weekly weight loss goals, and (4) combined process and outcome incentives. MEASURES/METHODS:Weight loss over a 16-week period; proportion who completed educational sessions; proportion who met weight loss goals. Analysis and Results: No intervention arm achieved greater reduction in weight than control (outcome incentive -6.6 lb [-9.1 to -4.1 lb], process incentive -7.3 lb [-9.5 to -5.1 lb], combined incentive -5.8 lb [-8.8 to -2.8 lb], control -7.9 lb [-11.1 to -4.7 lb]; all P > .29). Session attendance in the process incentive arm (50%) was significantly higher than control (31%; P < .0001) and combined incentive arms (28%; P < .0001), but not significantly higher than the outcome incentive arm (38%). CONCLUSION/CONCLUSIONS:Process incentives increased session attendance, but when combined at half strength with outcome incentives did not achieve that effect. There were no significant effects of either process or outcomes incentives on weight loss.

BACKGROUND:Black women are more likely to experience adverse effects from cancer treatment such as lymphedema. Thus, black women may particularly benefit from research regarding interventions to improve lymphedema. Herein, the authors report the challenges and strategies related to the recruitment of minority survivors of breast cancer and to the recruitment of survivors of breast cancer with lymphedema into the Women In Steady Exercise Research (WISER) Survivor Clinical Trial. METHODS:Subjects for this community-based trial were recruited from the Philadelphia area through active (mailings) and passive (printed materials and Web site) recruitment strategies. In addition, education sessions coordinated through partner hospitals in communities with a predominantly minority population were conducted to increase awareness of lymphedema in survivors of breast cancer. Women who were interested in the study were screened for lymphedema via telephone questionnaire and invited to see a study-related certified lymphedema therapist to confirm the presence of lymphedema. RESULTS:Screening was conducted among 2295 women: 628 were eligible, 450 consented, and 351 were randomized. Minority women comprised 38% of the study population. Letters to women on state and hospital registries resulted in a 0.4% randomization rate; education sessions yielded a 10% randomization rate. The authors observed that approximately 23.6% of the study sample had no previous diagnosis of lymphedema. CONCLUSIONS:The WISER Survivor Clinical Trial faced multiple recruitment challenges and used unique strategies to successfully enroll minority survivors of breast cancer into a lifestyle intervention. Cancer 2018;124:95-104. © 2017 American Cancer Society.