Association between diet quality and ovarian cancer risk and survival.

BACKGROUND: Research on diet quality and ovarian cancer is limited. We examined the association between diet quality and ovarian cancer risk and survival in a large prospective cohort. METHODS: We utilized data from women in the prospective NIH-AARP Diet and Health Study enrolled from 1995-1996 and were 50-71 years old at baseline with follow-up through 12/31/2017. Participants completed a 124-item Food Frequency Questionnaire at baseline and diet quality was assessed via the Healthy Eating Index-2015 (HEI-2015), the alternate Mediterranean diet score (aMED), and the Dietary Approaches to Stop Hypertension score (DASH). Primary outcomes were first primary epithelial ovarian cancer diagnosis from cancer registry data, and among those diagnosed with ovarian cancer all-cause mortality. We used a semi-Markov multi-state model with Cox proportional hazards regression to account for semi-competing events. RESULTS: Among 150,643 participants with a median follow-up time of 20.5 years, 1,107 individuals were diagnosed with a first primary epithelial ovarian cancer. There was no evidence of an association between diet quality and ovarian cancer risk. Among those diagnosed with epithelial ovarian cancer, 893 deaths occurred with a median survival of 2.5 years. Better pre-diagnosis diet quality, according to the HEI-2015 (Quintile 5 vs Quintile 1 HR = 0.75 [0.60-0.93]) and aMED (Quintile 5 vs Quintile 1: HR = 0.68, [0.53-0.87]) was associated with lower all-cause mortality. There was no evidence of an association between DASH and all-cause mortality. CONCLUSIONS: Better pre-diagnosis diet quality was associated with lower all-cause mortality after ovarian cancer diagnosis, but was not associated with ovarian cancer risk.

Alcohol Use and Sustained Virologic Response to Hepatitis C Virus Direct-Acting Antiviral Therapy.

Importance: Some payers and clinicians require alcohol abstinence to receive direct-acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) infection. Objective: To evaluate whether alcohol use at DAA treatment initiation is associated with decreased likelihood of sustained virologic response (SVR). Design, Setting, and Participants: This retrospective cohort study used electronic health records from the US Department of Veterans Affairs (VA), the largest integrated national health care system that provides unrestricted access to HCV treatment. Participants included all patients born between 1945 and 1965 who were dispensed DAA therapy between January 1, 2014, and June 30, 2018. Data analysis was completed in November 2020 with updated sensitivity analyses performed in 2023. Exposure: Alcohol use categories were generated using responses to the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) questionnaire and International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnoses for alcohol use disorder (AUD): abstinent without history of AUD, abstinent with history of AUD, lower-risk consumption, moderate-risk consumption, and high-risk consumption or AUD. Main Outcomes and Measures: The primary outcome was SVR, which was defined as undetectable HCV RNA for 12 weeks or longer after completion of DAA therapy. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% CIs of SVR associated with alcohol category. Results: Among 69 229 patients who initiated DAA therapy (mean [SD] age, 62.6 [4.5] years; 67 150 men [97.0%]; 34 655 non-Hispanic White individuals [50.1%]; 28 094 non-Hispanic Black individuals [40.6%]; 58 477 individuals [84.5%] with HCV genotype 1), 65 355 (94.4%) achieved SVR. A total of 32 290 individuals (46.6%) were abstinent without AUD, 9192 (13.3%) were abstinent with AUD, 13 415 (19.4%) had lower-risk consumption, 3117 (4.5%) had moderate-risk consumption, and 11 215 (16.2%) had high-risk consumption or AUD. After adjustment for potential confounding variables, there was no difference in SVR across alcohol use categories, even for patients with high-risk consumption or AUD (OR, 0.95; 95% CI, 0.85-1.07). There was no evidence of interaction by stage of hepatic fibrosis measured by fibrosis-4 score (P for interaction = .30). Conclusions and Relevance: In this cohort study, alcohol use and AUD were not associated with lower odds of SVR. Restricting access to DAA therapy according to alcohol use creates an unnecessary barrier to patients and challenges HCV elimination goals.

Effect of Exercise on Chemotherapy-Induced Peripheral Neuropathy Among Patients Treated for Ovarian Cancer: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Chemotherapy-induced peripheral neuropathy (CIPN), one of the most common and severe adverse effects of chemotherapy, is associated with worse quality of life among survivors of ovarian cancer. Currently, there is no effective treatment for CIPN. Objective: To evaluate the effect of a 6-month aerobic exercise intervention vs attention-control on CIPN among women treated for ovarian cancer in the Women's Activity and Lifestyle Study in Connecticut (WALC) to provide evidence to inform the guidelines and recommendations for prevention or treatment of CIPN. Design, Setting, and Participants: This prespecified secondary analysis evaluated the Women's Activity and Lifestyle Study in Connecticut (WALC), a multicentered, open-label, population-based, phase 3 randomized clinical trial of an aerobic exercise intervention vs attention control for CIPN in patients who were diagnosed with ovarian cancer. Only WALC participants who received chemotherapy were included in this analysis. Participants were randomized 1:1 to either a 6-month aerobic exercise intervention or to attention control. All analyses were conducted between September 2022 and January 2023. Interventions: The exercise intervention consisted of home-based moderate-intensity aerobic exercise facilitated by weekly telephone counseling from an American College of Sports Medicine/American Cancer Society-certified cancer exercise trainer. Attention control involved weekly health education telephone calls from a WALC staff member. Main Outcomes and Measure: Change in CIPN was the primary outcome in this secondary analysis. This outcome was represented by CIPN severity, which was self-measured by participants at baseline and 6 months using the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity scale, with a score range of 0 to 44. A mixed-effects model was used to assess the 6-month change in CIPN between the exercise intervention and attention control arms. Results: Of the 134 participants (all females; mean [SD] age, 57.5 [8.3] years) included in the analysis, 69 were in the exercise intervention arm and 65 were in the attention control arm. The mean (SD) time since diagnosis was 1.7 (1.0) years. The mean (SD) baseline CIPN scores were 8.1 (5.6) in the exercise intervention arm and 8.8 (7.9) in the attention control arm (P = .56). At 6 months, the self-reported CIPN score was reduced by 1.3 (95% CI, -2.3 to -0.2) points in the exercise intervention arm compared with an increase of 0.4 (95% CI, -0.8 to 1.5) points in the attention control arm. The between-group difference was -1.6 (95% CI, -3.1 to -0.2) points. The point estimate was larger among the 127 patients with CIPN symptoms at enrollment (-2.0; 95% CI, -3.6 to -0.5 points). Conclusions and Relevance: Findings of this secondary analysis of the WALC trial indicate that a 6-month aerobic exercise intervention vs attention control significantly improved self-reported CIPN among patients who were treated for ovarian cancer. While replication of the findings in other studies is warranted, incorporating referrals to exercise programs into standard oncology care could reduce CIPN symptoms and increase quality of life in patients with ovarian cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT02107066.

Structural Racism, Lifestyle Behaviors, and Obesity-related Cancers among Black and Hispanic/Latino Adults in the United States: A Narrative Review.

One in three adults in the United States has obesity; a chronic disease that is implicated in the etiology of at least 14 cancers. Cancer is the leading cause of death among U.S. Hispanic/Latino adults and the second most common cause of death, after cardiovascular disease, for Black adults. Our country's legacy in overt discrimination (e.g., slavery, segregation) generated inequities across all spheres in which people function as defined by the socioecological model-biological, individual, community, structural-and two of the many areas in which it manifests today are the disproportionate burden of obesity and obesity-related cancers in populations of color. Inequities due to environmental, social, and economic factors may predispose individuals to poor lifestyle behaviors by hindering an individual's opportunity to make healthy lifestyles choices. In this review, we examined the evidence on obesity and the lifestyle guidelines for cancer prevention in relation to cancer risk and outcomes for Black and Hispanic/Latino adults. We also discussed the role of structural and societal inequities on the ability of these two communities to adopt and maintain healthful lifestyle behaviors in accordance with the lifestyle guidelines for cancer prevention and control.

Rejection Sensitivity and Sexual Minority Men's Social Anxiety Disorder: The Moderating Role of Sexual Identity Strength.

Although gay-related rejection sensitivity (RS) is associated with social anxiety among sexual minority men, little attention has been given to the validity of gay-related RS measures and to individual differences that might moderate the association between gay-related RS and social anxiety. In a population-based sample of sexual minority men, Study 1 (N = 114) investigated the incremental validity of gay-related RS and showed that gay-related RS scores significantly added to the prediction of social anxiety symptoms, even after controlling for personal RS scores. In a clinical sample of sexual minority men, Study 2 (N = 254) examined interrelationships among gay-related RS, sexual identity strength, and current social anxiety symptoms and disorder diagnosis. Results revealed that the expected count of current social anxiety symptoms and the odds of social anxiety disorder diagnosis, as assessed with a structured diagnostic interview, increased as a function of gay-related RS scores. Sexual identity strength moderated these relationships, such that the associations between gay-related RS scores and interviewer-assessed social anxiety symptoms and disorder were only significant for those high, but not low, in sexual identity strength. Together, results from the present studies lend support to the incremental validity of gay-related RS scales in predicting social anxiety symptoms and suggest that sexual minority men who consider their sexual orientation to be self-defining might be particularly vulnerable to the mental health correlates of gay-related RS.

Phenotypes of disease severity in a cohort of hospitalized COVID-19 patients: Results from the IMPACC study.

BACKGROUND: Better understanding of the association between characteristics of patients hospitalized with coronavirus disease 2019 (COVID-19) and outcome is needed to further improve upon patient management. METHODS: Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) is a prospective, observational study of 1164 patients from 20 hospitals across the United States. Disease severity was assessed using a 7-point ordinal scale based on degree of respiratory illness. Patients were prospectively surveyed for 1 year after discharge for post-acute sequalae of COVID-19 (PASC) through quarterly surveys. Demographics, comorbidities, radiographic findings, clinical laboratory values, SARS-CoV-2 PCR and serology were captured over a 28-day period. Multivariable logistic regression was performed. FINDINGS: The median age was 59 years (interquartile range [IQR] 20); 711 (61%) were men; overall mortality was 14%, and 228 (20%) required invasive mechanical ventilation. Unsupervised clustering of ordinal score over time revealed distinct disease course trajectories. Risk factors associated with prolonged hospitalization or death by day 28 included age ≥ 65 years (odds ratio [OR], 2.01; 95% CI 1.28-3.17), Hispanic ethnicity (OR, 1.71; 95% CI 1.13-2.57), elevated baseline creatinine (OR 2.80; 95% CI 1.63- 4.80) or troponin (OR 1.89; 95% 1.03-3.47), baseline lymphopenia (OR 2.19; 95% CI 1.61-2.97), presence of infiltrate by chest imaging (OR 3.16; 95% CI 1.96-5.10), and high SARS-CoV2 viral load (OR 1.53; 95% CI 1.17-2.00). Fatal cases had the lowest ratio of SARS-CoV-2 antibody to viral load levels compared to other trajectories over time (p=0.001). 589 survivors (51%) completed at least one survey at follow-up with 305 (52%) having at least one symptom consistent with PASC, most commonly dyspnea (56% among symptomatic patients). Female sex was the only associated risk factor for PASC. INTERPRETATION: Integration of PCR cycle threshold, and antibody values with demographics, comorbidities, and laboratory/radiographic findings identified risk factors for 28-day outcome severity, though only female sex was associated with PASC. Longitudinal clinical phenotyping offers important insights, and provides a framework for immunophenotyping for acute and long COVID-19. FUNDING: NIH.

LGBQ-affirmative cognitive-behavioral therapy for young gay and bisexual men's mental and sexual health: A three-arm randomized controlled trial.

OBJECTIVE: Effective Skills to Empower Effective Men (ESTEEM) represents the first intervention to address the psychological pathways through which minority stress undermines young sexual minority men's (SMM's) mental and sexual health using transdiagnostic cognitive-behavioral therapy. This study compared the efficacy of ESTEEM against two existing interventions. METHOD: Participants were young HIV-negative SMM (N = 254; ages = 18-35; 67.2% racial/ethnic minority) experiencing a depression, anxiety, and/or stress-/trauma-related disorder and past-90-day HIV transmission risk behavior. After completing HIV testing and counseling, participants were randomized to receive 10-session ESTEEM (n = 100); 10-session community-based LGBQ-affirmative counseling (n = 102); or only HIV testing and counseling (n = 52). RESULTS: For the primary outcome of any HIV transmission risk behavior at 8 months, ESTEEM was not significantly associated with greater reduction compared to HIV testing and counseling (risk ratio [RR] = 0.89, p = .52). Supportive analyses of the frequency of HIV transmission risk behavior at 8 months showed a nonsignificant difference between ESTEEM compared to HIV testing and counseling (RR = 0.69) and LGBQ-affirmative counseling (RR = 0.62). For secondary outcomes (e.g., depression, anxiety, substance use, suicidality, number of mental health diagnoses) at 8 months, ESTEEM had a larger effect size than the two comparison conditions, but these comparisons did not reach statistical significance when adjusting for the false discovery rate. Observed effect sizes for condition comparisons were smaller than the effect sizes used to power the study. In exploratory analyses, ESTEEM showed promise for reducing comorbidity. CONCLUSIONS: Because the control conditions were associated with stronger effects than anticipated, and given the heterogeneous nature of transdiagnostic outcomes, the study possessed insufficient power to statistically detect the consistently small-to-moderate benefit of ESTEEM compared to the two control conditions. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Impact of complex, partially nested clustering in a three-arm individually randomized group treatment trial: A case study with the wHOPE trial.

BACKGROUND/AIMS: When participants in individually randomized group treatment trials are treated by multiple clinicians or in multiple group treatment sessions throughout the trial, this induces partially nested clusters which can affect the power of a trial. We investigate this issue in the Whole Health Options and Pain Education trial, a three-arm pragmatic, individually randomized clinical trial. We evaluate whether partial clusters due to multiple visits delivered by different clinicians in the Whole Health Team arm and dynamic participant groups due to changing group leaders and/or participants across treatment sessions during treatment delivery in the Primary Care Group Education arm may impact the power of the trial. We also present a Bayesian approach to estimate the intraclass correlation coefficients. METHODS: We present statistical models for each treatment arm of Whole Health Options and Pain Education trial in which power is estimated under different intraclass correlation coefficients and mapping matrices between participants and clinicians or treatment sessions. Power calculations are based on pairwise comparisons. In practice, sample size calculations depend on estimates of the intraclass correlation coefficients at the treatment sessions and clinician levels. To accommodate such complexities, we present a Bayesian framework for the estimation of intraclass correlation coefficients under different participant-to-session and participant-to-clinician mapping scenarios. We simulated continuous outcome data based on various clinical scenarios in Whole Health Options and Pain Education trial using a range of intraclass correlation coefficients and mapping matrices and used Gibbs samplers with conjugate priors to obtain posteriors of the intraclass correlation coefficients under those different scenarios. Posterior means and medians and their biases are calculated for the intraclass correlation coefficients to evaluate the operating characteristics of the Bayesian intraclass correlation coefficient estimators. RESULTS: Power for Whole Health Team versus Primary Care Group Education is sensitive to the intraclass correlation coefficient in the Whole Health Team arm. In these two arms, an increased number of clinicians, more evenly distributed workload of clinicians, or more homogeneous treatment group sizes leads to increased power. Our simulation study for the intraclass correlation coefficient estimation indicates that the posterior mean intraclass correlation coefficient estimator has less bias when the true intraclass correlation coefficients are large (i.e. 0.10), but when the intraclass correlation coefficient is small (i.e. 0.01), the posterior median intraclass correlation coefficient estimator is less biased. CONCLUSION: Knowledge of intraclass correlation coefficients and the structure of clustering are critical to the design of individually randomized group treatment trials with partially nested clusters. We demonstrate that the intraclass correlation coefficient of the Whole Health Team arm can affect power in the Whole Health Options and Pain Education trial. A Bayesian approach provides a flexible procedure for estimating the intraclass correlation coefficients under complex scenarios. More work is needed to educate the research community about the individually randomized group treatment design and encourage publication of intraclass correlation coefficients to help inform future trial designs.

Generation of parametric Ki images for FDG PET using two 5-min scans.

PURPOSE: The net uptake rate constant (Ki ) derived from dynamic imaging is considered the gold standard quantification index for FDG PET. In this study, we investigated the feasibility and assessed the clinical usefulness of generating Ki images for FDG PET using only two 5-min scans with population-based input function (PBIF). METHODS: Using a Siemens Biograph mCT, 10 subjects with solid lung nodules underwent a single-bed dynamic FDG PET scan and 13 subjects (five healthy and eight cancer patients) underwent a whole-body dynamic FDG PET scan in continuous-bed-motion mode. For each subject, a standard Ki image was generated using the complete 0-90 min dynamic data with Patlak analysis (t* = 20 min) and individual patient's input function, while a dual-time-point Ki image was generated from two 5-min scans based on the Patlak equations at early and late scans with the PBIF. Different start times for the early (ranging from 20 to 55 min with an increment of 5 min) and late (ranging from 50 to 85 min with an increment of 5 min) scans were investigated with the interval between scans being at least 30 min (36 protocols in total). The optimal dual-time-point protocols were then identified. Regions of interest (ROI) were drawn on nodules for the lung nodule subjects, and on tumors, cerebellum, and bone marrow for the whole-body-imaging subjects. Quantification accuracy was compared using the mean value of each ROI between standard Ki (gold standard) and dual-time-point Ki , as well as between standard Ki and relative standardized uptake value (SUV) change that is currently used in clinical practice. Correlation coefficients and least squares fits were calculated for each dual-time-point protocol and for each ROI. Then, the predefined criteria for identifying a reliable dual-time-point Ki estimation for each ROI were empirically determined as: (1) the squared correlation coefficient (R2 ) between standard Ki and dual-time-point Ki is larger than 0.9; (2) the absolute difference between the slope of the equality line (1.0) and that of the fitted line when plotting standard Ki versus dual-time-point Ki is smaller than 0.1; (3) the absolute value of the intercept of the fitted line when plotting standard Ki versus dual-time-point Ki normalized by the mean of the standard Ki across all subjects for each ROI is smaller than 10%. Using Williams' one-tailed t test, the correlation coefficient (R) between standard Ki and dual-time-point Ki was further compared with that between standard Ki and relative SUV change, for each dual-time-point protocol and for each ROI. RESULTS: Reliable dual-time-point Ki images were obtained for all the subjects using our proposed method. The percentage error introduced by the PBIF on the dual-time-point Ki estimation was smaller than 1% for all 36 protocols. Using the predefined criteria, reliable dual-time-point Ki estimation could be obtained in 25 of 36 protocols for nodules and in 34 of 36 protocols for tumors. A longer time interval between scans provided a more accurate Ki estimation in general. Using the protocol of 20-25 min plus 80-85 or 85-90 min, very high correlations were obtained between standard Ki and dual-time-point Ki (R2  = 0.994, 0.980, 0.971 and 0.925 for nodule, tumor, cerebellum, and bone marrow), with all the slope values with differences ≤0.033 from 1 and all the intercept values with differences ≤0.0006 mL/min/cm3 from 0. The corresponding correlations were much lower between standard Ki and relative SUV change (R2  = 0.673, 0.684, 0.065, 0.246). Dual-time-point Ki showed a significantly higher quantification accuracy with respect to standard Ki than relative SUV change for all the 36 protocols (p < 0.05 using Williams' one-tailed t test). CONCLUSIONS: Our proposed approach can obtain reliable Ki images and accurate Ki quantification from dual-time-point scans (5-min per scan), and provide significantly higher quantification accuracy than relative SUV change that is currently used in clinical practice.

A case study of ascertainment bias for the primary outcome in the Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE) trial.

BACKGROUND/AIM: In clinical trials, there is potential for bias from unblinded observers that may influence ascertainment of outcomes. This issue arose in the Strategies to Reduce Injuries and Develop Confidence in Elders trial, a cluster randomized trial to test a multicomponent intervention versus enhanced usual care (control) to prevent serious fall injuries, originally defined as a fall injury leading to medical attention. An unblinded nurse falls care manager administered the intervention, while the usual care arm did not involve contact with a falls care manager. Thus, there was an opportunity for falls care managers to refer participants reporting falls to seek medical attention. Since this type of observer bias could not occur in the usual care arm, there was potential for additional falls to be reported in the intervention arm, leading to dilution of the intervention effect and a reduction in study power. We describe the clinical basis for ascertainment bias, the statistical approach used to assess it, and its effect on study power. METHODS: The prespecified interim monitoring plan included a decision algorithm for assessing ascertainment bias and adapting (revising) the primary outcome definition, if necessary. The original definition categorized serious fall injuries requiring medical attention into Type 1 (fracture other than thoracic/lumbar vertebral, joint dislocation, cut requiring closure) and Type 2 (head injury, sprain or strain, bruising or swelling, other). The revised definition, proposed by the monitoring plan, excluded Type 2 injuries that did not necessarily require an overnight hospitalization since these would be most subject to bias. These injuries were categorized into those with (Type 2b) and without (Type 2c) medical attention. The remaining Type 2a injuries required medical attention and an overnight hospitalization. We used the ratio of 2b/(2b + 2c) in intervention versus control as a measure of ascertainment bias; ratios > 1 indicated the likelihood of falls care manager bias. We determined the effect of ascertainment bias on study power for the revised (Types 1 and 2a) versus original definition (Types 1, 2a, and 2b). RESULTS: The estimate of ascertainment bias was 1.14 (95% confidence interval: 0.98, 1.30), providing evidence of the likelihood of falls care manager bias. We estimated that this bias diluted the hazard ratio from the hypothesized 0.80 to 0.86 and reduced power to under 80% for the original primary outcome definition. In contrast, adapting the revised definition maintained study power at nearly 90%. CONCLUSION: There was evidence of ascertainment bias in the Strategies to Reduce Injuries and Develop Confidence in Elders trial. The decision to adapt the primary outcome definition reduced the likelihood of this bias while preserving the intervention effect and study power.

Correction to: Excess Weight Gain After Cure of Hepatitis C Infection with Direct-Acting Antivirals.

JGIM published the article matched with the editorial in this issue in the July 2020 issue. Our apologies to the authors of the paper and the editorial.

Two-stage randomized trial design for testing treatment, preference, and self-selection effects for count outcomes.

While the traditional clinical trial design lays emphasis on testing the treatment effect between randomly assigned groups, it ignores the role of patient preference for a particular treatment in the trial. Yet, for healthcare providers who seek to optimize the patient-centered treatment strategy, the evaluation of a patient's psychology toward each treatment could be a key consideration. The two-stage randomized trial design allows researchers to test patient's preference and selection effects, in addition to the treatment effect. The current methodology for the two-stage design is limited to continuous and binary outcomes; this article extends the model to include count outcomes. The test statistics for preference, selection, and treatment effects are derived. Closed-form sample size formulae are presented for each effect. Simulations are presented to demonstrate the properties of the unstratified and stratified designs. Finally, we apply methods to the use of antimicrobials at the end of life to demonstrate the applicability of the methods.

Excess Weight Gain After Cure of Hepatitis C Infection with Direct-Acting Antivirals.

BACKGROUND: Cure from chronic hepatitis C virus (HCV) infection is readily achievable with direct-acting antivirals (DAA), but little is known about optimal management after treatment. Weight gained after DAA treatment may mitigate benefits or increase risk for liver disease progression. As the single largest sample of HCV-infected individuals receiving DAA treatment in the United States, the Veterans Affairs (VA) Birth Cohort is an ideal setting to assess weight gain after DAA treatment. METHODS: We performed a prospective study of patients dispensed DAA therapy from January 2014 to June 2015. Weight change was calculated as the difference in weight from sustained virologic response (SVR) determination to 2 years later. Demographic, weight, height, prescription, laboratory, and diagnosis code data were used for covariate definitions. We used multiple logistic regression to assess the association between candidate predictors and excess weight gain (≥ 10 lbs) after 2 years. RESULTS: Among 11,469 patients, 78.0% of patients were already overweight or obese at treatment initiation. Overall, SVR was achieved in 97.0% of patients. After 2 years, 52.6% of patients gained weight and 19.8% gained excess weight. In those with SVR, weight gain was as high as 38.2 lbs, with the top 10% gaining ≥ 16.5 lbs. Only 1% of those with obesity at treatment initiation normalized their weight class after 2 years. Significant predictors of post-SVR weight gain were SVR achievement, lower age, high FIB-4 score, cirrhosis, and weight class at treatment initiation. CONCLUSION: Weight gain is common after DAA treatment, even among those who are overweight or obese prior to treatment. Major predictors include age, baseline weight, alcohol, cirrhosis, and SVR. Everyone receiving DAAs should be counseled against weight gain with a particular emphasis among those at higher risk.

Project ESTEEM protocol: a randomized controlled trial of an LGBTQ-affirmative treatment for young adult sexual minority men's mental and sexual health.

BACKGROUND: Young gay and bisexual men disproportionately experience depression, anxiety, and substance use problems and are among the highest risk group for HIV infection in the U.S. Diverse methods locate the source of these health disparities in young gay and bisexual men's exposure to minority stress. In fact, minority stress, psychiatric morbidity, substance use, and HIV risk fuel each other, forming a synergistic threat to young gay and bisexual men's health. Yet no known intervention addresses minority stress to improve mental health, substance use problems, or their joint impact on HIV risk in this population. This paper describes the design of a study to test the efficacy of such an intervention, called ESTEEM (Effective Skills to Empower Effective Men), a 10-session skills-building intervention designed to reduce young gay and bisexual men's co-occurring health risks by addressing the underlying cognitive, affective, and behavioral pathways through which minority stress impairs health. METHODS: This study, funded by the National Institute of Mental Health, is a three-arm randomized controlled trial to examine (1) the efficacy of ESTEEM compared to community mental health treatment and HIV counseling and testing and (2) whether ESTEEM works through its hypothesized cognitive, affective, and behavioral minority stress processes. Our primary outcome, measured 8 months after baseline, is condomless anal sex in the absence of PrEP or known undetectable viral load of HIV+ primary partners. Secondary outcomes include depression, anxiety, substance use, sexual compulsivity, and PrEP uptake, also measured 8 months after baseline. DISCUSSION: Delivering specific stand-alone treatments for specific mental, behavioral, and sexual health problems represents the current state of evidence-based practice. However, dissemination and implementation of this one treatment-one problem approach has not been ideal. A single intervention that reduces young gay and bisexual men's depression, anxiety, substance use, and HIV risk by reducing the common minority stress pathways across these problems would represent an efficient, cost-effective alternative to currently isolated approaches, and holds great promise for reducing sexual orientation health disparities among young men. TRIAL REGISTRATION: Registered October 10, 2016 to ClinicalTrials.gov Identifier: NCT02929069 .

Screening, Recruitment, and Baseline Characteristics for the Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE) Study.

Background: We describe the recruitment of participants for Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE), a large pragmatic cluster randomized trial that is testing the effectiveness of a multifactorial intervention to prevent serious fall injuries. Eligible persons were 70 years or older, community-living, and at increased risk for serious fall injuries. The modified goal was to recruit 5,322 participants over 20 months from 86 primary care practices within 10 diverse health care systems across the United States. Methods: The at-risk population was identified using two distinct but complementary screening strategies that included three questions administered centrally via the mail (nine sites) or in the clinic (one site), while recruitment was completed centrally by staff at Yale. Results: For central screening, 226,603 letters mailed to 135,118 patients yielded 28,719 positive screens (12.7% of those mailed and 46.5% of the 61,729 returned). In the clinic, 22,537 screens were completed, leading to 5,732 positive screens (25.4%). Of the 34,451 patients who screened positive for high risk of serious fall injuries, 31,872 were sent a recruitment packet and, of these, 5,451 (17.1%) were enrolled over 20 months (mean age: 80 years; 62% female). The participation rate was 34.0% among eligible patients. The enrollment yields were 3.6% (vs 5% projected) for each patient screened centrally, despite multiple screens, and 10.5% (vs 33.9% projected) for each positive clinic screen. Conclusions: Despite lower-than-expected yields, the STRIDE Study exceeded its modified recruitment goal. If the STRIDE intervention is found to be effective, the two distinct strategies for identifying a high-risk population of older persons could be implemented by most health care systems.

Simplified Quantification and Acquisition Protocol for 123I-MIBG Dynamic SPECT.

Previous studies have demonstrated the feasibility of absolute quantification of dynamic 123I-metaiodobenzylguanidine (123I-MIBG) SPECT imaging in humans. This work reports a simplified quantification method for dynamic 123I-MIBG SPECT using practical protocols with shortened acquisition time and voxel-by-voxel parametric imaging. Methods: Twelve healthy human volunteers underwent five 15-min dynamic SPECT scans at 0, 15, 90, 120, and 180 min after 123I-MIBG injection. List-mode SPECT data were binned into 29 frames and reconstructed with corrections for attenuation, scatter, and decay. Population-based blood-to-plasma correction and metabolite correction were applied to the image-derived input function. Likelihood estimation in graphical analysis (LEGA) was used as a simplified model to obtain volume of distribution (VT) values, which were compared with those obtained with the reversible 2-tissue (2T) compartment model. Three simplified protocols were evaluated with 2T and LEGA using a 30-min scan started simultaneously with tracer injection plus a 15-min scan at 90, 120, or 180 min after injection. Voxel-by-voxel LEGA fitting was applied to the aligned dynamic images using both the full protocol (five 15-min scans) and the simplified protocols. Results: Correlation analysis (y = 0.955x + 0.547, R2 = 0.997) and Bland-Altman plot (mean difference, -0.8 mL/cm3; 95% limits of agreement, [-2.5, 1.0] mL/cm3; normal VT range, 29.0 ± 12.4 mL/cm3) showed that LEGA can be used as a simplified model of 2T for 123I-MIBG. High-quality VT parametric images could be obtained with LEGA. Region-of-interest (ROI) modeling and parametric imaging results were in excellent agreement as determined by correlation analysis (y = 0.999x - 1.026, R2 = 0.982) and Bland-Altman plot (mean difference, -1.0 mL/cm3; 95% limits of agreement, [-4.2, 2.1] mL/cm3). VT correlated reasonably well between all simplified protocols and the full protocol with LEGA but not with 2T. The VT results were more reliable when there was a longer interval between the 2 acquisitions in the simplified protocols. Conclusion: For ROI-based kinetic modeling and parametric imaging, reliable quantification of dynamic 123I-MIBG SPECT can be achieved with LEGA using a simplified protocol of a 30-min scan starting with tracer injection plus a 15-min scan no earlier than 180 min after injection.

Sample size and power for a stratified doubly randomized preference design.

The two-stage (or doubly) randomized preference trial design is an important tool for researchers seeking to disentangle the role of patient treatment preference on treatment response through estimation of selection and preference effects. Up until now, these designs have been limited by their assumption of equal preference rates and effect sizes across the entire study population. We propose a stratified two-stage randomized trial design that addresses this limitation. We begin by deriving stratified test statistics for the treatment, preference, and selection effects. Next, we develop a sample size formula for the number of patients required to detect each effect. The properties of the model and the efficiency of the design are established using a series of simulation studies. We demonstrate the applicability of the design using a study of Hepatitis C treatment modality, specialty clinic versus mobile medical clinic. In this example, a stratified preference design (stratified by alcohol/drug use) may more closely capture the true distribution of patient preferences and allow for a more efficient design than a design which ignores these differences (unstratified version).

An Initiative to Improve the Quality of Care of Infants With Neonatal Abstinence Syndrome.

BACKGROUND AND OBJECTIVES: The incidence of neonatal abstinence syndrome (NAS), a constellation of neurologic, gastrointestinal, and musculoskeletal disturbances associated with opioid withdrawal, has increased dramatically and is associated with long hospital stays. At our institution, the average length of stay (ALOS) for infants exposed to methadone in utero was 22.4 days before the start of our project. We aimed to reduce ALOS for infants with NAS by 50%. METHODS: In 2010, a multidisciplinary team began several plan-do-study-act cycles at Yale New Haven Children's Hospital. Key interventions included standardization of nonpharmacologic care coupled with an empowering message to parents, development of a novel approach to assessment, administration of morphine on an as-needed basis, and transfer of infants directly to the inpatient unit, bypassing the NICU. The outcome measures included ALOS, morphine use, and hospital costs using statistical process control charts. RESULTS: There were 287 infants in our project, including 55 from the baseline period (January 2008 to February 2010) and 44 from the postimplementation period (May 2015 to June 2016). ALOS decreased from 22.4 to 5.9 days. Proportions of methadone-exposed infants treated with morphine decreased from 98% to 14%; costs decreased from $44 824 to $10 289. No infants were readmitted for treatment of NAS and no adverse events were reported. CONCLUSIONS: Interventions focused on nonpharmacologic therapies and a simplified approach to assessment for infants exposed to methadone in utero led to both substantial and sustained decreases in ALOS, the proportion of infants treated with morphine, and hospital costs with no adverse events.

Disparities in hepatitis C testing in U.S. veterans born 1945-1965.

BACKGROUND & AIMS: Universal one-time antibody testing for hepatitis C virus (HCV) infection has been recommended by the centers for disease control (CDC) and the United States preventative services task force (USPSTF) for Americans born 1945-1965 (birth cohort). Limited data exists addressing national HCV testing practices. We studied patterns and predictors of HCV testing across the U.S. within the birth cohort utilizing data from the national corporate data warehouse of the U.S. Veterans Administration (VA) health system. METHODS: Testing was defined as any HCV test including antibody, RNA or genotype performed during 2000-2013. RESULTS: Of 6,669,388 birth cohort veterans, 4,221,135 (63%) received care within the VA from 2000-2013 with two or more visits. Of this group, 2,139,935 (51%) had HCV testing with 8.1% HCV antibody and 5.4% RNA positive. Significant variation in testing was observed across centers (range: 7-83%). Older, male, African-Americans, with established risk factors and receiving care from urban centers of excellence were more likely to be tested. Among veterans free of other established risk factors (HIV negative, HBV negative, ALT ⩽40U/L, FIB-4 ⩽1.45, or APRI <0.5), HCV antibody and RNA were positive in 2.8% and 0.9%, respectively, comparable to established national average. At least 2.4-4.4% of veterans had scores suggesting advanced fibrosis (APRI ⩾1.5 or FIB-4 >3.25) with >30-43% having positive HCV RNA but >16-20% yet to undergo testing for HCV. CONCLUSIONS: Significant disparities are observed in HCV testing within the United States VA health system. Examination of the predictors of testing and HCV positivity may help inform national screening policies. LAY SUMMARY: Analysis of United States Veterans Administration data show significant disparities in hepatitis C virus testing of veterans born 1945-1965 (birth cohort). A fifth of those not tested had evidence of advanced liver fibrosis. Our data suggests some predictors for this disparity and will potentially help inform future policy measures in the era of universal birth cohort testing for HCV.