Casting New Light on Statistical Power: An Illuminating Analogy and Strategies to Avoid Underpowered Trials.

Current standards for methodological rigor and trial reporting underscore the critical issue of statistical power. Still, the chance of detecting most effects reported in randomized controlled trials in medicine and other disciplines is currently lower than winning a toss of a fair coin. Here we propose that investigators who retain a practical understanding of how statistical power works can proactively avoid the potentially devastating consequences of underpowered trials. We first offer a vivid, carefully constructed analogy that illuminates the underlying relationships among 3 of the 5 essential parameters-namely, statistical power, effect size, and sample size-while holding the remaining 2 parameters constant (type of statistical test and significance level). Second, we extend the analogy to a set of critical scenarios in which investigators commonly miss detecting intervention effects due to insufficient statistical power. Third, we highlight effective pragmatic strategies for the design and conduct of sufficiently powered trials, without increasing sample size.

Outreach to diversify clinical trial participation: A randomized recruitment study.

BACKGROUND/AIMS: Racial and ethnic minorities remain underrepresented in clinical research, yet few recruitment strategies have been rigorously evaluated. METHODS: We experimentally tested whether targeted recruitment letters acknowledging diabetes health disparities and health risks specific to recipients' racial/ethnic group improved two metrics of trial participation: willingness to be screened and enrollment. This experiment was efficiently nested within a randomized clinical trial examining a preventive lifestyle intervention among women at high risk for diabetes. Pregnant women with gestational diabetes or impaired glucose tolerance (N = 445) were randomized to receive a targeted recruitment letter with health risk information specific to their racial/ethnic group (n = 216), or a standard letter with risk information for the general population (n = 229). All letters were bilingual in English and Spanish. RESULTS: The targeted as compared to the standard letter did not improve screening or enrollment rates overall or within separate racial/ethnic groups. Among Latina women who preferred Spanish, the targeted letter showed trends for improved screening (66.7% vs 33.3%, p = .06) and enrollment rates (38.9% vs 13.3%, p = .13). In contrast, among Latina women who preferred English, the targeted letter significantly lowered screening (29.6% vs 57.1%, p = .04) and showed trends for lowered enrollment rates (25.9% vs 50.0%, p = .07). CONCLUSION: Results from this randomized study appear to suggest that recruitment letters with diabetes health risk information targeted to recipients' race/ethnicity may improve one metric of clinical trial participation among Latina women who prefer Spanish, but not English. Larger experimental studies, incorporating input from diverse participant stakeholders, are needed to develop evidence-based minority recruitment strategies.

Intrinsic motivation for physical activity, healthy eating, and self-weighing in association with corresponding behaviors in early pregnancy.

Healthy lifestyle behaviors influence maternal cardiovascular health, but motivation for them in pregnancy is poorly understood. We examined whether intrinsic motivation (assessed on 5-point scales for each behavior) is associated with three lifestyle behaviors in early pregnancy: physical activity, by intensity level; healthy eating, quantified with the Alternate Healthy Eating Index for Pregnancy (AHEI-P); and weight self-monitoring, a standard weight management technique. Participants in the Northern California Pregnancy, Lifestyle and Environment Study (PETALS) population-based cohort completed validated surveys in early pregnancy (2017-18; N = 472; 22 % Asian, 6 % Black, 30 % Hispanic, 13 % multiracial, 30 % White). Cross-sectional data were analyzed in 2021-22. Overall, 40.7 % (n = 192) met United States national physical activity guidelines; the average AHEI-P score was 62.3 out of 130 (SD 11.4); and 36.9 % reported regular self-weighing (≥once/week; n = 174). In models adjusted for participant characteristics, 1-unit increases in intrinsic motivation were associated with increased likelihood of meeting physical activity guidelines (risk ratio [95 % CI]: 1.66 [1.48, 1.86], p < 0.0001); meeting sample-specific 75th percentiles for vigorous physical activity (1.70 [1.44, 1.99], p < 0.0001) and AHEI-P (1.75 [1.33, 2.31], p < 0.0001); and regular self-weighing (2.13 [1.92, 2.37], p < 0.0001). A 1-unit increase in intrinsic motivation lowered the risk of meeting the 75th percentile for sedentary behavior (0.79 [0.67, 0.92], p < 0.003). Intrinsic motivation was not associated with reaching 75th percentiles for total, light, or moderate activity. Intrinsic motivation is associated with physical activity, healthy eating, and self-weighing among diverse individuals in early pregnancy. Results can inform intervention design to promote maternal health via increased enjoyment of lifestyle behaviors.

Momentary Influences on Self-Regulation in Two Populations With Health Risk Behaviors: Adults Who Smoke and Adults Who Are Overweight and Have Binge-Eating Disorder.

Introduction: Self-regulation has been implicated in health risk behaviors and is a target of many health behavior interventions. Despite most prior research focusing on self-regulation as an individual-level trait, we hypothesize that self-regulation is a time-varying mechanism of health and risk behavior that may be influenced by momentary contexts to a substantial degree. Because most health behaviors (e.g., eating, drinking, smoking) occur in the context of everyday activities, digital technologies may help us better understand and influence these behaviors in real time. Using a momentary self-regulation measure, the current study (which was part of a larger multi-year research project on the science of behavior change) used ecological momentary assessment (EMA) to assess if self-regulation can be engaged and manipulated on a momentary basis in naturalistic, non-laboratory settings. Methods: This one-arm, open-label exploratory study prospectively collected momentary data for 14 days from 104 participants who smoked regularly and 81 participants who were overweight and had binge-eating disorder. Four times per day, participants were queried about momentary self-regulation, emotional state, and social and environmental context; recent smoking and exposure to smoking cues (smoking sample only); and recent eating, binge eating, and exposure to binge-eating cues (binge-eating sample only). This study used a novel, momentary self-regulation measure comprised of four subscales: momentary perseverance, momentary sensation seeking, momentary self-judgment, and momentary mindfulness. Participants were also instructed to engage with Laddr, a mobile application that provides evidence-based health behavior change tools via an integrated platform. The association between momentary context and momentary self-regulation was explored via mixed-effects models. Exploratory assessments of whether recent Laddr use (defined as use within 12 h of momentary responses) modified the association between momentary context and momentary self-regulation were performed via mixed-effects models. Results: Participants (mean age 35.2; 78% female) in the smoking and binge-eating samples contributed a total of 3,233 and 3,481 momentary questionnaires, respectively. Momentary self-regulation subscales were associated with several momentary contexts, in the combined as well as smoking and binge-eating samples. For example, in the combined sample momentary perseverance was associated with location, positively associated with positive affect, and negatively associated with negative affect, stress, and tiredness. In the smoking sample, momentary perseverance was positively associated with momentary difficulty in accessing cigarettes, caffeine intake, and momentary restraint in smoking, and negatively associated with temptation and urge to smoke. In the binge-eating sample, momentary perseverance was positively associated with difficulty in accessing food and restraint in eating, and negatively associated with urge to binge eat. While recent Laddr use was not associated directly with momentary self-regulation subscales, it did modify several of the contextual associations, including challenging contexts. Conclusions: Overall, this study provides preliminary evidence that momentary self-regulation may vary in response to differing momentary contexts in samples from two exemplar populations with risk behaviors. In addition, the Laddr application may modify some of these relationships. These findings demonstrate the possibility of measuring momentary self-regulation in a trans-diagnostic way and assessing the effects of momentary, mobile interventions in context. Health behavior change interventions may consider measuring and targeting momentary self-regulation in addition to trait-level self-regulation to better understand and improve health risk behaviors. This work will be used to inform a later stage of research focused on assessing the transdiagnostic mediating effect of momentary self-regulation on medical regimen adherence and health outcomes. Clinical Trial Registration: ClinicalTrials.gov, Identifier: NCT03352713.

Downstream funding success of early career researchers for resubmitted versus new applications: A matched cohort.

BACKGROUND: Early career researchers face a hypercompetitive funding environment. To help identify effective intervention strategies for early career researchers, we examined whether first-time NIH R01 applicants who resubmitted their original, unfunded R01 application were more successful at obtaining any R01 funding within 3 and 5 years than original, unfunded applicants who submitted new NIH applications, and we examined whether underrepresented minority (URM) applicants differentially benefited from resubmission. Our observational study is consistent with an NIH working group's recommendations to develop interventions to encourage resubmission. METHODS AND FINDINGS: First-time applicants with US medical school academic faculty appointments who submitted an unfunded R01 application between 2000-2014 yielded 4,789 discussed and 7,019 not discussed applications. We then created comparable groups of first-time R01 applicants (resubmitted original R01 application or submitted new NIH applications) using optimal full matching that included applicant and application characteristics. Primary and subgroup analyses used generalized mixed models with obtaining any NIH R01 funding within 3 and 5 years as the two outcomes. A gamma sensitivity analysis was performed. URM applicants represented 11% and 12% of discussed and not discussed applications, respectively. First-time R01 applicants resubmitting their original, unfunded R01 application were more successful obtaining R01 funding within 3 and 5 years than applicants submitting new applications-for both discussed and not discussed applications: discussed within 3 years (OR 4.17 [95 CI 3.53, 4.93]) and 5 years (3.33 [2.82-3.92]); and not discussed within 3 years (2.81 [2.52, 3.13]) and 5 years (2.47 [2.22-2.74]). URM applicants additionally benefited within 5 years for not discussed applications. CONCLUSIONS: Encouraging early career researchers applying as faculty at a school of medicine to resubmit R01 applications is a promising potential modifiable factor and intervention strategy. First-time R01 applicants who resubmitted their original, unfunded R01 application had log-odds of obtaining downstream R01 funding within 3 and 5 years 2-4 times higher than applicants who did not resubmit their original application and submitted new NIH applications instead. Findings held for both discussed and not discussed applications.

Introducing the MAVEN Leadership Training Initiative to diversify the scientific workforce.

Addressing gender and racial-ethnic disparities at all career stages is a priority for the research community. In this article, we focus on efforts to encourage mid-career women, particularly women of color, to move into leadership positions in science and science policy. We highlight the need to strengthen leadership skills for the critical period immediately following promotion to associate/tenured professor - when formal career development efforts taper off while institutional demands escalate - and describe a program called MAVEN that has been designed to teach leadership skills to mid-career women scientists, particularly those from underrepresented groups.

Methods-Motivational Interviewing Approach for Enhanced Retention and Attendance.

INTRODUCTION: Suboptimal and differential participant engagement in randomized trials-including retention at primary outcome assessments and attendance at intervention sessions-undermines rigor, internal validity, and trial conclusions. METHODS: First, this study describes Methods-Motivational Interviewing approach and strategies for implementation. This approach engages potential participants before randomization through interactive, prerequisite orientation sessions that illustrate the scientific rationale behind trial methods in accessible language and use motivational interviewing to diffuse ambivalence about participation. Then, this study examines the potential improvements in retention (proportion of participants assessed at follow-up visits) and attendance (e.g., mean percentage of intervention sessions attended, percentage of participants who attended 0 sessions) in 3 randomized weight-management trials that quickly added prerequisite orientations to their protocols following early signs of suboptimal or differential participant engagement (Supporting Health by Integrating Nutrition and Exercise [2009-2013, n=194]; Get Social [2016-2020, n=217]; GestationaL Weight Gain and Optimal Wellness [2014-2018, n=389]). Using a pre-post analytical design, adjusted estimates from regression models controlling for condition and assessment timepoint (analyses from 2020) are reported. RESULTS: After adding prerequisite orientations, all 3 trials attained higher participant engagement. Retention at assessments was 11.4% and 17.3% higher (Get Social and Supporting Health by Integrating Nutrition and Exercise, respectively). Mean percentage of attendance at intervention sessions was 8.8% higher (GestationaL Weight Gain and Optimal Wellness), and 10.1% fewer participants attended 0 intervention sessions (Get Social). Descriptively, all the remaining retention and attendance outcomes were consistently higher but were nonsignificant. Across the trials, adding prerequisite orientations did not impact the proportion of eligible participants enrolled or the baseline demographics. CONCLUSIONS: The Methods-Motivational Interviewing approach shows promise for increasing the rigor of randomized trials and is readily adaptable to in-person, webinar, and conference call formats. TRIAL REGISTRATION: All 3 trials are registered at www.clinicaltrials.gov (Supporting Health by Integrating Nutrition and Exercise: NCT00960414; Get Social: NCT02646618; and GestationaL Weight Gain and Optimal Wellness: NCT02130232).

Interactive group-based orientation sessions: A method to improve adherence and retention in pragmatic clinical trials.

BACKGROUND: Intervention adherence and trial retention are challenging for clinical trials testing intensive behavioral interventions. Operational constraints or trial designs may preclude using effective retention strategies such as financial incentives. We examined whether implementing pre-enrollment orientation sessions was associated with higher intervention adherence and retention in a pragmatic clinical trial. METHODS: The trial tested an intensive behavioral intervention for patients with chronic pain on long-term opioids. Orientation sessions were implemented two years into trial recruitment at one site. Held before informed consent and randomization, these mandatory, group-based orientation sessions provided trial specifics, explained research methods principles, and leveraged motivational interviewing techniques. Using a pre-post design and multivariate models, we assessed adherence (number of intervention meetings attended) and retention (completed quarterly pain assessments over 12 months) before (04/2014-12/2015; n = 209) and after (01/2016-02/2017; n = 258) implementation. Also, we evaluated whether session implementation affected the proportion and characteristics of enrolled patients. RESULTS: After implementing orientation sessions, patients had higher intervention adherence than before (M = 7.6, SD = 3.8 vs. M = 5.6, SD = 4.5, respectively; mean difference = 2.0, 95% CI [0.9, 3.2], p = .001), and 2.8 times greater odds of completing quarterly assessments (95% CI [1.3, 5.8], p = .007). Fewer patients enrolled after implementing sessions than before (38.1% vs. 70.8%, 95% CI [26.4, 39.1], p < .001), with no differences in patient characteristics. CONCLUSIONS: Implementing orientation sessions during recruitment may be useful for promoting trial adherence and retention. To ensure enrollment goals are met, target population size and barriers affecting patients' ability to attend orientation sessions should be considered, especially for patients with complex medical conditions. CLINICAL TRIALS REGISTRATION NUMBER: NCT02113592.

Challenges and Opportunities for the Prevention and Treatment of Cardiovascular Disease Among Young Adults: Report From a National Heart, Lung, and Blood Institute Working Group.

Improvements in cardiovascular disease (CVD) rates among young adults in the past 2 decades have been offset by increasing racial/ethnic and gender disparities, persistence of unhealthy lifestyle habits, overweight and obesity, and other CVD risk factors. To enhance the promotion of cardiovascular health among young adults 18 to 39 years old, the medical and broader public health community must understand the biological, interpersonal, and behavioral features of this life stage. Therefore, the National Heart, Lung, and Blood Institute, with support from the Office of Behavioral and Social Science Research, convened a 2-day workshop in Bethesda, Maryland, in September 2017 to identify research challenges and opportunities related to the cardiovascular health of young adults. The current generation of young adults live in an environment undergoing substantial economic, social, and technological transformations, differentiating them from prior research cohorts of young adults. Although the accumulation of clinical and behavioral risk factors for CVD begins early in life, and research suggests early risk is an important determinant of future events, few trials have studied prevention and treatment of CVD in participants <40 years old. Building an evidence base for CVD prevention in this population will require the engagement of young adults, who are often disconnected from the healthcare system and may not prioritize long-term health. These changes demand a repositioning of existing evidence-based treatments to accommodate new sociotechnical contexts. In this article, the authors review the recent literature and current research opportunities to advance the cardiovascular health of today's young adults.

Concerns about infertility risks among pediatric oncology patients and their parents.

BACKGROUND: Given pediatric cancer patients are living into adulthood, parents and patients need to be informed about fertility-related side effects of their particular treatment. PROCEDURE: We surveyed 97 parents of pediatric patients of all ages as well as 37 adolescent patients of 14 years or older who were presented for care at the Lucile Packard Children's Hospital (LPCH) at the Stanford University Medical Center. We estimated the potential infertility risk (low, intermediate, and high) based on the child's treatment regimen. RESULTS: In contrast to our hypothesis, the majority of parents in all three risk categories were concerned about fertility-related side effects of cancer treatment. Many parents with children at low risk were concerned (58.3%) whereas not all parents with children at intermediate or high risk were concerned, 61.5% and 73.3% respectively, P = 0.43. Indeed, over 50% of all parents were erroneously concerned that cancer therapies cause DNA damage to their child's eggs (or sperm). Only 29.9% of parents were satisfied with the amount of information received. Similar patterns were seen among the adolescent patient sample. CONCLUSIONS: Parents of pediatric cancer patients and teenage patients have concerns about fertility-related side effects regardless of treatment received. Targeted education about infertility risk before and after treatment can address these gaps.

Effects of a methodological infographic on research participants' knowledge, transparency, and trust.

OBJECTIVE: Given participants' research literacy is essential for clinical trial participation, evidence-based strategies are needed that improve literacy and easily accessed online. We tested whether an infographic letter-that illustrated how dropouts can distort study conclusions-improved participant knowledge about the impact of dropouts relative to a control letter. METHOD: In three distinct online samples purposely recruited to assess reproducibility, young ethnically diverse adults were randomized to read an infographic letter or control letter in a hypothetical scenario. Secondary outcomes included participants' perceived transparency of the research organization, perceived value of retention, and perceived trust of the organization. We purposely included two discriminant items, perceived value for the trial outcome and keeping commitments in general, both hypothesized not to change. RESULTS: Across samples, ∼20% more infographic participants correctly answered how dropouts affected study conclusions than control participants. For example (Experiment 3), nearly 90% of infographic participants correctly answered versus only two thirds of controls (88.7% vs. 66.7%, absolute percentage difference 22.0%, p < .0001). Infographic participants had substantially higher transparency, perceived value for retention, and trust (Cohen's ds = 0.4-1.0, ps < .0001), yet importantly did not value the study outcome or report keeping commitments more than control participants (Cohen's ds = 0.0-0.1, ps > .10). CONCLUSIONS: Promisingly, this transparent, visually powerful methodological infographic improved knowledge and trust. Future trials could embed and experimentally test whether such low-cost online infographics improve not only research literacy, but also trial retention, especially among populations with less initial trust about research. (PsycINFO Database Record

The Relationship Between the Stanford Leisure-Time Activity Categorical Item and the Godin Leisure-Time Exercise Questionnaire Among Rural Intervention Participants of Varying Health Literacy Status.

BACKGROUND: A pragmatic, self-reported physical activity measure is needed for individuals of varying health literacy status. METHODS: This study is a secondary analysis of a 6-month behavioral intervention for rural Appalachian adults developed using health literacy strategies. We examined the relationship and responsiveness of the Stanford Leisure-Time Activity Categorical Item (L-Cat) and adapted Godin Leisure-Time Exercise Questionnaire (GLTEQ) and determined if baseline health literacy status moderates intervention effects. RESULTS: Of 301 enrolled participants, 289 completed the L-Cat at baseline and 212 at 6 months. Approximately 33% were low health literate and 43% reported annual income of ≤$14,999. There was high agreement (84.1%) between the L-Cat and adapted GLTEQ for classifying individuals as meeting physical activity recommendations with little differences by health literacy level (low literacy 80.4% and high literacy 85.9%). The primary source of incongruent classification was the adapted GLTEQ classified almost 20% of individuals as meeting recommendations, whereas the L-Cat classified them as not meeting recommendations. There were differences in responsiveness between measures, but baseline health literacy status did not moderate change in any L-Cat or adapted GLTEQ measures. CONCLUSION: Implications and recommendations for using the L-Cat 2.3 and GLTEQ among individuals of varying health literacy status are discussed.

Applying novel technologies and methods to inform the ontology of self-regulation.

Self-regulation is a broad construct representing the general ability to recruit cognitive, motivational and emotional resources to achieve long-term goals. This construct has been implicated in a host of health-risk behaviors, and is a promising target for fostering beneficial behavior change. Despite its clear importance, the behavioral, psychological and neural components of self-regulation remain poorly understood, which contributes to theoretical inconsistencies and hinders maximally effective intervention development. We outline a research program that seeks to define a neuropsychological ontology of self-regulation, articulating the cognitive components that compose self-regulation, their relationships, and their associated measurements. The ontology will be informed by two large-scale approaches to assessing individual differences: first purely behaviorally using data collected via Amazon's Mechanical Turk, then coupled with neuroimaging data collected from a separate population. To validate the ontology and demonstrate its utility, we will then use it to contextualize health risk behaviors in two exemplar behavioral groups: overweight/obese adults who binge eat and smokers. After identifying ontological targets that precipitate maladaptive behavior, we will craft interventions that engage these targets. If successful, this work will provide a structured, holistic account of self-regulation in the form of an explicit ontology, which will better clarify the pattern of deficits related to maladaptive health behavior, and provide direction for more effective behavior change interventions.

Image-guided robotic radiosurgery for spinal metastases.

BACKGROUND AND PURPOSE: To determine the effectiveness and safety of image-guided robotic radiosurgery for spinal metastases. MATERIALS/METHODS: From 1996 to 2005, 74 patients with 102 spinal metastases were treated using the CyberKnife at Stanford University. Sixty-two (84%) patients were symptomatic. Seventy-four percent (50/68) of previously treated patients had prior radiation. Using the CyberKnife, 16-25 Gy in 1-5 fractions was delivered. Patients were followed clinically and radiographically for at least 3 months or until death. RESULTS: With mean follow-up of 9 months (range 0-33 months), 36 patients were alive and 38 were dead at last follow-up. No death was treatment related. Eighty-four (84%) percent of symptomatic patients experienced improvement or resolution of symptoms after treatment. Three patients developed treatment-related spinal injury. Analysis of dose-volume parameters and clinical parameters failed to identify predictors of spinal cord injury. CONCLUSIONS: Robotic radiosurgery is effective and generally safe for spinal metastases even in previously irradiated patients.

The ASIBS Short Course: A unique strategy for increasing statistical competency of junior investigators in academic medicine.

As clinical researchers at academic medical institutions across the United States increasingly manage complex clinical databases and registries, they often lack the statistical expertise to utilize the data for research purposes. This statistical inadequacy prevents junior investigators from disseminating clinical findings in peer-reviewed journals and from obtaining research funding, thereby hindering their potential for promotion. Underrepresented minorities, in particular, confront unique challenges as clinical investigators stemming from a lack of methodologically rigorous research training in their graduate medical education. This creates a ripple effect for them with respect to acquiring full-time appointments, obtaining federal research grants, and promotion to leadership positions in academic medicine. To fill this major gap in the statistical training of junior faculty and fellows, the authors developed the Applied Statistical Independence in Biological Systems (ASIBS) Short Course. The overall goal of ASIBS is to provide formal applied statistical training, via a hybrid distance and in-person learning format, to junior faculty and fellows actively involved in research at US academic medical institutions, with a special emphasis on underrepresented minorities. The authors present an overview of the design and implementation of ASIBS, along with a short-term evaluation of its impact for the first cohort of ASIBS participants.

Impact of a Genetic Risk Score for Coronary Artery Disease on Reducing Cardiovascular Risk: A Pilot Randomized Controlled Study.

PURPOSE: We tested whether providing a genetic risk score (GRS) for coronary artery disease (CAD) would serve as a motivator to improve adherence to risk-reducing strategies. METHODS: We randomized 94 participants with at least moderate risk of CAD to receive standard-of-care with (N = 49) or without (N = 45) their GRS at a subsequent 3-month follow-up visit. Our primary outcome was change in low density lipoprotein cholesterol (LDL-C) between the 3- and 6-month follow-up visits (ΔLDL-C). Secondary outcomes included other CAD risk factors, weight loss, diet, physical activity, risk perceptions, and psychological outcomes. In pre-specified analyses, we examined whether there was a greater motivational effect in participants with a higher GRS. RESULTS: Sixty-five participants completed the protocol including 30 participants in the GRS arm. We found no change in the primary outcome between participants receiving their GRS and standard-of-care participants (ΔLDL-C: -13 vs. -9 mg/dl). Among participants with a higher GRS, we observed modest effects on weight loss and physical activity. All other secondary outcomes were not significantly different, including anxiety and worry. CONCLUSION: Adding GRS to standard-of-care did not change lipids, adherence, or psychological outcomes. Potential modest benefits in weight loss and physical activity for participants with high GRS need to be validated in larger trials.

A Simulation Modeling Framework to Optimize Programs Using Financial Incentives to Motivate Health Behavior Change.

INTRODUCTION: While increasingly popular among mid- to large-size employers, using financial incentives to induce health behavior change among employees has been controversial, in part due to poor quality and generalizability of studies to date. Thus, fundamental questions have been left unanswered: To generate positive economic returns on investment, what level of incentive should be offered for any given type of incentive program and among which employees? METHODS: We constructed a novel modeling framework that systematically identifies how to optimize marginal return on investment from programs incentivizing behavior change by integrating commonly collected data on health behaviors and associated costs. We integrated "demand curves" capturing individual differences in response to any given incentive with employee demographic and risk factor data. We also estimated the degree of self-selection that could be tolerated: that is, the maximum percentage of already-healthy employees who could enroll in a wellness program while still maintaining positive absolute return on investment. In a demonstration analysis, the modeling framework was applied to data from 3000 worksite physical activity programs across the nation. RESULTS: For physical activity programs, the incentive levels that would optimize marginal return on investment ($367/employee/year) were higher than average incentive levels currently offered ($143/employee/year). Yet a high degree of self-selection could undermine the economic benefits of the program; if more than 17% of participants came from the top 10% of the physical activity distribution, the cost of the program would be expected to always be greater than its benefits. DISCUSSION: Our generalizable framework integrates individual differences in behavior and risk to systematically estimate the incentive level that optimizes marginal return on investment.

Sentinel lymph node biopsy for cutaneous melanoma: the Stanford experience, 1997-2004.

OBJECTIVE: To review sentinel lymph node (SLN) data from Stanford University Medical Center from January 1, 1997, to January 1, 2004, including rates of SLN positivity according to 2002 American Joint Committee on Cancer (AJCC) tumor classification, relation to other clinical and pathologic prognostic factors, and rates and sites of melanoma recurrence. DESIGN: Retrospective case series. SETTING: Stanford University Medical Center and Stanford melanoma clinics. PATIENTS: A total of 274 consecutive patients with primary melanoma who underwent SLN biopsy (SLNB) between January 1, 1997, and January 1, 2004, or who were referred to the Stanford melanoma clinics after SLNB and were followed up through March 2005. INTERVENTIONS: All patients underwent standard wide local excision of their primary tumors and SLNB with intradermal injection of isosulfan blue dye and/or technetium sulfur colloid. MAIN OUTCOME MEASURE: Rates of SLN positivity per 2002 AJCC tumor classification, relation to other clinical and pathologic prognostic factors, and rates and sites of melanoma recurrence in node-negative and node-positive patients. RESULTS: Positive SLNs were detected in 39 (15%) of 260 cases, including 0 (0%) of 45 for cutaneous melanomas 1.0 mm thick or less (T1), 21 (18%) of 115 for melanomas 1.01 to 2.0 mm thick (T2), 12 (19%) of 64 for melanomas 2.01 to 4.0 mm thick (T3), and 5 (16%) of 32 for melanomas thicker than 4.0 mm (T4). Median Breslow depths were 1.89 mm for SLN-positive biopsy specimens and 1.50 mm for SLN-negative biopsy specimens (P = .07). The recurrence rate was 46% among SLN-positive patients, with a median time to recurrence of 8 months. Bivariate analysis revealed SLN positivity to be associated with AJCC tumor classification (P = .02), location on the trunk (P = .03), and presence of ulceration (P = .03). By multivariate logistic regression, ulceration (P = .01) was predictive of SLN positivity, whereas SLN status (P< .001), ulceration (P = .02), and location (P = .03) were predictive of recurrent disease. CONCLUSION: Data from the past 8 years confirm the accuracy and prognostic value of SLNB in cutaneous melanoma and the low rate of regional nodal recurrence for SLN-negative patients.

Putting the brakes on the "drive to eat": Pilot effects of naltrexone and reward-based eating on food cravings among obese women.

PURPOSE: Obese individuals vary in their experience of food cravings and tendency to engage in reward-driven eating, both of which can be modulated by the neural reward system rather than physiological hunger. We examined two predictions in a sample of obese women: (1) whether opioidergic blockade reduced food-craving intensity, and (2) whether opioidergic blockade reduced an association between food-craving intensity and reward-driven eating, which is a trait-like index of three factors (lack of control over eating, lack of satiation, preoccupation with food). METHODS: Forty-four obese, pre-menopausal women completed the Reward-Based Eating Drive (RED) scale at study start and daily food-craving intensity on 5 days on which they ingested either a pill-placebo (2 days), a 25 mg naltrexone dose (1 day), or a standard 50mg naltrexone dose (2 days). RESULTS: Craving intensity was similar under naltrexone and placebo doses. The association between food-craving intensity and reward-driven eating significantly differed between placebo and 50mg naltrexone doses. Reward-driven eating and craving intensity were significantly positively associated under both placebo doses. As predicted, opioidergic blockade (for both doses 25mg and 50mg naltrexone) reduced the positive association between reward-driven eating and craving intensity to non-significance. CONCLUSIONS: Opioidergic blockade did not reduce craving intensity; however, blockade reduced an association between trait-like reward-driven eating and daily food-craving intensity, and may help identify an important endophenotype within obesity.

Promoting healthy weight with "stability skills first": a randomized trial.

OBJECTIVE: Although behavioral weight-loss interventions produce short-term weight loss, long-term maintenance remains elusive. This randomized trial examined whether learning a novel set of "stability skills" before losing weight improved long-term weight management. Stability skills were designed to optimize individuals' current satisfaction with lifestyle and self-regulatory habits while requiring the minimum effort and attention necessary. METHOD: Overweight/obese women (N = 267) were randomly assigned to one of two 6-month interventions and assessed at baseline and at 6, 12, and 18 months. Maintenance First women participated first in an 8-week stability skills maintenance module and then in a standard 20-week behavioral weight-loss program. Weight Loss First women participated first in a standard 20-week behavioral weight-loss program and then in a standard 8-week problem-solving skills maintenance module. There was no intervention staff contact during the 12-month follow-up period (6-18 months). RESULTS: As designed, Maintenance First participants lost the same percentage of initial weight during the 6-month intervention period as Weight Loss First participants (M = -8.6%, SD = 5.7, vs. M = -9.1%, SD = 6.9; t = -0.6, p = .52). However, Maintenance First participants regained significantly less weight during the 12-month follow-up period (6-18 months) than Weight Loss First participants (M = 3.2 lb, SD = 10.4, vs. M = 7.3 lb, SD = 9.9 [M = 1.4 kg, SD = 4.7, vs. M = 3.3 kg, SD = 4.5]; t = 3.3, p = .001, d = 0.4). CONCLUSION: Learning stability skills before losing weight was successful in helping women to maintain weight loss without intervention staff contact during follow-up. These results can inform the study design of future innovative interventions.