Bayesian single-to-double arm transition design using both short-term and long-term endpoints.

The choice between single-arm designs versus randomized double-arm designs has been contentiously debated in the literature of phase II oncology trials. Recently, as a compromise, the single-to-double arm transition design was proposed, combining the two designs into one trial over two stages. Successful implementation of the two-stage transition design requires a suspension period at the end of the first stage to collect the response data of the already enrolled patients. When the evaluation of the primary efficacy endpoint is overly long, the between-stage suspension period may unfavorably prolong the trial duration and cause a delay in treating future eligible patients. To accelerate the trial, we propose a Bayesian single-to-double arm design with short-term endpoints (BSDS), where an intermediate short-term endpoint is used for making early termination decisions at the end of the single-arm stage, followed by an evaluation of the long-term endpoint at the end of the subsequent double-arm stage. Bayesian posterior probabilities are used as the primary decision-making tool at the end of the trial. Design calibration steps are proposed for this Bayesian monitoring process to control the frequentist operating characteristics and minimize the expected sample size. Extensive simulation studies have demonstrated that our design has comparable power and average sample size but a much shorter trial duration than conventional single-to-double arm design. Applications of the design are illustrated using two phase II oncology trials with binary endpoints.

Prevalence and trends in urinary incontinence among women in the United States, 2005-2018.

BACKGROUND: Women are disproportionately affected by urinary incontinence compared with men. Urinary incontinence results in physical and psychological adverse consequences and impaired quality of life and contributes to significant societal and economic burden. Previous studies reported high urinary incontinence burden in the United States. However, the current prevalence and recent trends in urinary incontinence and its subtypes among US women have not been described. In addition, correlates of urinary incontinence among US women have not been systematically evaluated in the contemporary population. OBJECTIVE: The purpose of this study was to determine the prevalence and trends in urinary incontinence among adult women in the United States from 2005 to 2018. In addition, this study aimed to investigate the relationship of urinary incontinence subtypes with several sociodemographic, lifestyle, health-related, and gynecologic factors. STUDY DESIGN: We used data from the National Health and Nutrition Examination Survey, a nationally representative series of surveys that was designed to evaluate the health status of the US population. Data on urinary incontinence from 7 consecutive 2-year cycles (2005-2006 to 2017-2018) were used for this study. A total of 19,791 participants aged ≥20 years were included. Weighted prevalence estimates and 95% confidence intervals were calculated in each study cycle for stress, urgency, and mixed urinary incontinence. Multivariate-adjusted weighted logistic regression was used to investigate the temporal trends in urinary incontinence, in addition to determining the association between urinary incontinence subtypes with several participants' factors. RESULTS: In the 2017-2018 cycle, stress urinary incontinence was the most prevalent subtype (45.9%; 95% confidence interval, 42.1-49.7), followed by urgency urinary incontinence (31.1%; 95% confidence interval, 28.6-33.6) and mixed urinary incontinence (18.1%; 95% confidence interval, 15.7-20.5). The prevalence rates of urgency and mixed urinary incontinence were higher in women aged 60 years and older (urgency, 49.5% [95% confidence interval, 43.9-55.2]; mixed, 31.4% [95% confidence interval, 26.2-36.6]) than in those aged 40 to 59 years (urgency, 27.9% [95% confidence interval, 23.6-32.1]; mixed, 15.9% [95% confidence interval, 12.9-19.0]) and those aged 20 to 39 years (urgency, 17.6% [95% confidence interval, 13.8-21.5]; mixed, 8.3% [95% confidence interval, 5.4-11.3]). The overall prevalence of stress and mixed urinary incontinence was stable throughout 2005 to 2018 (both Ptrend=.3), with increases in mixed urinary incontinence among women aged 60 years and older (P=.001). The prevalence of urgency urinary incontinence significantly increased, particularly among women aged 60 years and older (both P=.002). Age, obesity, smoking, comorbidities, and postmenopausal hormone therapy were associated with higher prevalence of all types of urinary incontinence. Black women were less likely to report stress urinary incontinence but more likely to report urgency urinary incontinence. CONCLUSION: Although the estimated overall prevalence of stress and mixed urinary incontinence remained stable from 2005 to 2018, the prevalence of urgency and mixed urinary incontinence significantly increased among women aged 60 years and older. All subtypes of urinary incontinence were higher among women with obesity and comorbidities, those who used postmenopausal hormone therapy, and those who smoke.

Regular Coffee Consumption Is Associated with Lower Regional Adiposity Measured by DXA among US Women.

BACKGROUND: Coffee is among the most popular daily beverages in the United States. Importantly, coffee consumption has been associated with a lower risk of multiple health outcomes including a reduction in adiposity. DXA is a means to assess body fat and distribution. OBJECTIVES: The aim of this study was to examine the relation between coffee consumption and DXA-assessed adiposity and adiposity distribution. METHODS: Cross-sectional data from the NHANES were used. Participants were adults aged 20-69 y from the 2003-2004 and 2005-2006 waves. Information on coffee consumption was assessed through the FFQ (categorized as no coffee, 0 to <0.25 cup/d, 0.25 to <1 cup/d, 1 cup/d, 2-3 cups/d, or ≥4 cups/d). Both caffeinated and decaffeinated coffee consumption were included. Trunk fat and total fat percentage were measured via whole-body DXA scans. The association between coffee consumption and body fat was investigated using age-adjusted and multivariable-adjusted linear regression models which accounted for sample weights. RESULTS: Higher coffee consumption was associated with significantly lower total body fat percentage and trunk body fat percentage in a dose-response manner (all P values < 0.05) among women. Although this dose-response relation was nonsignificant among men, men aged 20-44 y who drank 2-3 cups/d had 1.3% (95% CI: -2.7%, 0.1%) less total fat and 1.8% (95% CI: -3.3%, -0.4%) less trunk fat than those who did not consume coffee. Furthermore, the association between coffee consumption and body fat percentage exhibited for both caffeinated and decaffeinated coffee among women (all P for trend < 0.001) but not among men (all P for trend > 0.05). CONCLUSIONS: The present study found a significant association between higher coffee consumption and lower DXA-measured adiposity. Moreover, a gender difference in this association in the general US adult population was also observed.

Trends in Sexual Activity and Associations With All-Cause and Cause-Specific Mortality Among US Adults.

BACKGROUND: Sexual activity can be referred to as a health behavior and may also act as an indicator of health status. AIM: To evaluate temporal trends in sexual activity and to examine associations of sexual activity with all-cause and cause-specific mortality risk. METHODS: We examined the trends and prevalence of sexual activity and association of sexual activity with all-cause and cause-specific mortality in a nationally representative sample using data from the US National Health and Nutrition Examination Survey from 2005 to 2016 and the National Health and Nutrition Examination Survey 2005-2014 Linked Mortality File (through December 31, 2015). OUTCOMES: All-cause, cardiovascular disease, and cancer mortality. RESULTS: A total of 15,269 US adults (mean age, 39.1 years [standard error, 0.18 years]) were included in the trend analysis. In the 2015-2016 cycle, while 71.7% (95% CI, 67.7-75.7%) US adults aged 20-59 years engaged in sexual activity ≥ 12 times/year (monthly), only 36.1% (95% CI, 31.6-40.7%) of them engaged in sexual activity ≥ 52 times/year (weekly). Since the 2005-2006 cycle, the estimated prevalence of sexual activity, ≥52 times/year and ≥12 times/year, were both stable over time among overall and each age group (all P for trend >0.1). During a median follow-up of 5.7 years (range, 1-11 years) and 71,960 person-years of observation, among 12,598 participants with eligible information on mortality status, 228 deaths occurred, including 29 associated with cardiovascular disease and 62 associated with cancer. Overall, participants with higher sexual activity frequency were at a lower risk of all-cause death in a dose-response manner (P for trend = 0.020) during the follow-up period. In addition, the multivariable-adjusted hazard ratios for all-cause mortality, CVD mortality, cancer mortality, and other cause mortality among participants who had sex ≥52 times/year compared with those having sex 0-1 time/year were 0.51 (95% CI, 0.34 to 0.76), 0.79 (95% CI, 0.19 to 3.21), 0.31 (95% CI, 0.11 to 0.84), and 0.52 (95% CI, 0.28 to 0.96), respectively. CLINICAL IMPLICATIONS: Sexual activity appears to be a health indicator of all-cause and cancer mortality in US middle-aged adults. STRENGTHS & LIMITATIONS: Clear strengths of the present study include the large representative sample of the noninstitutionalized US population as well as the identification of precise estimates in relation to sexual activity and mortality. However, because of the observational nature of the study design, causality could not be determined. CONCLUSIONS: Sexual activity was found to be associated with a lower risk of mortality from all cause and cancer. Cao C, Yang L, Xu T, et al. Trends in Sexual Activity and Associations With All-Cause and Cause-Specific Mortality Among US Adults. J Sex Med 2020;17:1903-1913.

Changes in whole body pain intensity and widespreadness during urologic chronic pelvic pain syndrome flares-Findings from one site of the MAPP study.

OBJECTIVE: To investigate changes in whole body pain during urologic chronic pelvic pain syndrome (UCPPS) flares. MATERIALS AND METHODS: UCPPS participants at one site of the multidisciplinary approach to the study of chronic pelvic pain research network reported their daily flare status and pain levels in 7 pelvic/genital and 42 extrapelvic body areas (scale = 0-10) for 10 days at baseline and during their first flare. Linear mixed models and conditional logistic regression were used to investigate symptom changes during flares. Analyses were stratified by chronic overlapping pain condition (COPC) status. RESULTS: Fifty-five out of 60 participants completed the study, 27 of whom provided information on both nonflare (n = 281) and flare (n = 208) days. Pelvic/genital pain intensity (mean change = 3.20 of 10) and widespreadness (mean = 1.48) increased significantly during flares for all participants (all P interaction > .1), whereas extrapelvic pain intensity increased significantly only among participants with COPCs (mean = 2.09; P interaction < .0001). Pelvic/genital and extrapelvic pain also varied on nonflare days but symptom fluctuations were generally ≤1 point (80.0%-100% of participants). Increases of ≥2 points in pelvic/genital pain intensity (odds ratio (OR) = 22.0, 95% confidence interval (CI) = 4.0-118.6) and ≥1 point in urination-related pain (OR = 9.10, 95% CI = 1.74-47.7) were independently associated with flare onset for all participants. CONCLUSION: Our observations of extrapelvic pain increases during flares for patients with COPCs and our independent associations between pelvic/genital/urination-related pain intensity and flare onset may provide insight into mechanisms underlying flare development (eg, common biologic pathways between UCPPS phenotypes and flares), flare management (eg, local vs systemic therapies by COPC status), and patient flare definitions.

Analysis of vitamin E metabolites including carboxychromanols and sulfated derivatives using LC/MS/MS.

Tocopherols and tocotrienols are metabolized via hydroxylation and oxidation of their hydrophobic side chain to generate 13'-hydroxychromanols (13'-OHs) and various carboxychromanols, which can be further metabolized by conjugation including sulfation. Recent studies indicate that long-chain carboxychromanols, especially 13'-carboxychromanol (13'-COOH), appear to be more bioactive than tocopherols in anti-inflammatory and anticancer actions. To understand the potential contribution of metabolites to vitamin E-mediated effects, an accurate assay is needed to evaluate bioavailability of these metabolites. Here we describe an LC/MS/MS assay for quantifying vitamin E metabolites using negative polarity ESI. This assay includes a reliable sample extraction procedure with efficacy of ≥ 89% and interday/intraday variation of 3-11% for major metabolites. To ensure accurate quantification, short-chain, long-chain, and sulfated carboxychromanols are included as external/internal standards. Using this assay, we observed that sulfated carboxychromanols are the primary metabolites in the plasma of rodents fed with γ-tocopherol or δ-tocopherol. Although plasma levels of 13'-COOHs and 13'-OHs are low, high concentrations of these compounds are found in feces. Our study demonstrates an LC/MS/MS assay for quantitation of sulfated and unconjugated vitamin E metabolites, and this assay will be useful for evaluating the role of these metabolites in vivo.

Association Between Symptom Burden and Early Lymphatic Abnormalities After Regional Nodal Irradiation for Breast Cancer.

PURPOSE: Dermal backflow visualized on near-infrared fluorescence lymphatic imaging (NIRF-LI) signals preclinical lymphedema that precedes the development of volumetrically defined lymphedema. We sought to evaluate whether dermal backflow correlates with patient-reported lymphedema outcomes (PRLO) surveys in breast cancer patients treated with regional nodal irradiation (RNI). METHODS AND MATERIALS: Patients with breast cancer planned for axillary dissection and RNI prospectively underwent perometry, NIRF-LI, and PRLOs (the Lymphedema Symptom Intensity and Distress Survey [LSIDS] and QuickDASH) at baseline, after surgery, and at 6, 12, and 18 months after radiation. Clinical lymphedema was defined as an arm volume increase ≥5% over baseline. Trends over time were assessed using analysis of variance testing. The association between survey responses and both dermal backflow and lymphedema was assessed using a linear mixed-effects model. RESULTS: Sixty participants completed at least 2 sets of measurements and surveys and were eligible for analysis. Fifty-four percent of patients had cT3-T4 disease, 53% cN3 disease, and 75% had a body mass index >25. Dermal backflow and clinical lymphedema increased from 10% to 85% and from 0% to 40%, respectively, from baseline to 18 months. In the adjusted model, soft tissue sensation, neurologic sensation, and functional LSIDS subscale scores were associated with presence of dermal backflow (all P < .05). Both dermal backflow and lymphedema were associated with QuickDASH score (P < .05). CONCLUSIONS: In this high-risk cohort, we found highly prevalent early signs of lymphedema, with increased symptom burden from baseline. Presence of dermal backflow correlated with PRLO measures, highlighting a potential NIRF-LI use to identify patients for early intervention trials after RNI.

Identification of Key Elements in Prostate Cancer for Ontology Building via a Multidisciplinary Consensus Agreement.

BACKGROUND: Clinical data collection related to prostate cancer (PCa) care is often unstructured or heterogeneous among providers, resulting in a high risk for ambiguity in its meaning when sharing or analyzing data. Ontologies, which are shareable formal (i.e., computable) representations of knowledge, can address these challenges by enabling machine-readable semantic interoperability. The purpose of this study was to identify PCa-specific key data elements (KDEs) for standardization in clinic and research. METHODS: A modified Delphi method using iterative online surveys was performed to report a consensus agreement on KDEs by a multidisciplinary panel of 39 PCa specialists. Data elements were divided into three themes in PCa and included (1) treatment-related toxicities (TRT), (2) patient-reported outcome measures (PROM), and (3) disease control metrics (DCM). RESULTS: The panel reached consensus on a thirty-item, two-tiered list of KDEs focusing mainly on urinary and rectal symptoms. The Expanded Prostate Cancer Index Composite (EPIC-26) questionnaire was considered most robust for PROM multi-domain monitoring, and granular KDEs were defined for DCM. CONCLUSIONS: This expert consensus on PCa-specific KDEs has served as a foundation for a professional society-endorsed, publicly available operational ontology developed by the American Association of Physicists in Medicine (AAPM) Big Data Sub Committee (BDSC).

Prospective, early longitudinal assessment of lymphedema-related quality of life among patients with locally advanced breast cancer: The foundation for building a patient-centered screening program.

BACKGROUND: We examined how breast cancer-related lymphedema (BCRL) affects health-related quality of life (HRQOL), productivity, and compliance with therapeutic interventions to guide structuring BCRL screening programs. METHODS: We prospectively followed consecutive breast cancer patients who underwent axillary lymph node dissection (ALND) with arm volume screening and measures assessing patient-reported health-related quality of life (HRQOL) and perceptions of BCRL care. Comparisons by BCRL status were made with Mann-Whitney U, Chi-square, Fisher's exact, or t tests. Trends over time from ALND were assessed with linear mixed-effects models. RESULTS: With a median follow-up of 8 months in 247 patients, 46% self-reported ever having BCRL, a proportion that increased over time. About 73% reported fear of BCRL, which was stable over time. Further in time from ALND, patients were more likely to report that BCRL screening reduced fear. Patient-reported BCRL was associated with higher soft tissue sensation intensity, biobehavioral, and resource concerns, absenteeism, and work/activity impairment. Objectively measured BCRL had fewer associations with outcomes. Most patients reported performing prevention exercises, but compliance decreased over time; patient-reported BCRL was not associated with exercise frequency. Fear of BCRL was positively associated with performing prevention exercises and using compressive garments. CONCLUSIONS: Both incidence and fear of BCRL were high after ALND for breast cancer. Fear was associated with improved therapeutic compliance, but compliance decreased over time. Patient-reported BCRL was more strongly associated with worse HRQOL and productivity than was objective BCRL. Screening programs must support patients' psychological needs and aim to sustain long-term compliance with recommended interventions.

Temporal characterization of acute pain and toxicity kinetics during radiation therapy for head and neck cancer. A retrospective study.

Objectives: Pain during Radiation Therapy (RT) for oral cavity/oropharyngeal cancer (OC/OPC) is a clinical challenge due to its multifactorial etiology and variable management. The objective of this study was to define complex pain profiles through temporal characterization of pain descriptors, physiologic state, and RT-induced toxicities for pain trajectories understanding. Materials and methods: Using an electronic health record registry, 351 OC/OPC patients treated with RT from 2013 to 2021 were included. Weekly numeric scale pain scores, pain descriptors, vital signs, physician-reported toxicities, and analgesics were analyzed using linear mixed effect models and Spearman's correlation. Area under the pain curve (AUCpain) was calculated to measure pain burden over time. Results: Median pain scores increased from 0 during the weekly visit (WSV)-1 to 5 during WSV-7. By WSV-7, 60% and 74% of patients reported mouth and throat pain, respectively, with a median pain score of 5. Soreness and burning pain peaked during WSV-6/7 (51%). Median AUCpain was 16% (IQR (9.3-23)), and AUCpain significantly varied based on gender, tumor site, surgery, drug use history, and pre-RT pain. A temporal increase in mucositis and dermatitis, declining mean bodyweight (-7.1%; P < 0.001) and mean arterial pressure (MAP) 6.8 mmHg; P < 0.001 were detected. Pulse rate was positively associated while weight and MAP were negatively associated with pain over time (P < 0.001). Conclusion: This study provides insight on in-depth characterization and associations between dynamic pain, physiologic, and toxicity kinetics. Our findings support further needs of optimized pain control through temporal data-driven clinical decision support systems for acute pain management.

Trends and Racial Disparities in the Prevalence of Urinary Incontinence Among Men in the USA, 2001-2020.

BACKGROUND: Male urinary incontinence (UI) affects quality of life and leads to a significant burden to the health care system. However, the contemporary prevalence and recent trends in UI and its subtypes among US men remain unknown. OBJECTIVE: We evaluated 20-yr trends in the prevalence of UI and its subtype in US men aged ≥20 yr. DESIGN, SETTING, AND PARTICIPANTS: A serial, cross-sectional analysis of the US nationally representative data from the National Health and Nutrition Examination Survey among men from 2001 to 2020. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Prevalence of any, stress, urgency and overflow UI were derived. The frequency of UI was assessed in four categories: less than one time per month, a few times per month, a few times per week, and every day and/or night. All analyses were conducted using sample weights, stratification, and clustering of the complex sampling design. Sociodemographic and lifestyle correlates of UI over time were identified using multivariable logistic regressions. RESULTS AND LIMITATIONS: Data on 22994 US men (mean age, 46.6 yr [standard error, 0.20]; weighted population, 848642150) were analyzed. The prevalence of any UI increased from 2001-2002 (11.5% [95% confidence interval {CI}, 10.0-13.0]) to 2017-2020 (19.3% [95% CI, 17.2-21.3]), driven by urgency (from 9.0% [95% CI, 7.5-10.4]) to 15.2% [95% CI, 13.4-16.9]) and overflow UI (from 3.3% [95% CI, 2.7-4.0] to 5.5% [95% CI, 4.5-6.4]; all p for trend < 0.01). UI affects 38.5% US men ≥60 yr of age, with increasing trends in urgency and overflow UI and a decreasing trend in stress UI (all p for trend < 0.05). Racial/ethnic disparities were noted, with patterns differed by UI subtype. Compared with non-Hispanic White, non-Hispanic Black men were more likely to report urgency UI (odds ratio [OR], 1.94 [95% CI, 1.71-2.20]). Hispanic men were more likely to report urgency UI (OR, 1.33 [95% CI, 1.14-1.56]), but less likely to report stress (OR, 0.74 [95% CI, 0.56-0.98]) and overflow (OR, 0.75 [95% CI, 0.58-0.98]) UI. Men with higher body mass index and current smokers were more likely to report any, stress, and urgency UI than their counterparts. A higher prevalence of any UI was found in men with low family poverty ratios and chronic diseases, and those who were physically inactive. CONCLUSIONS: From 2001 to 2020, the overall prevalence of UI increased among US men, particularly for urgency and overflow UI. PATIENT SUMMARY: In this report, we looked at the prevalence of urinary incontinence among US men in a nationally representative sample. We found that urinary incontinence increased in the past 20 yr driving by the urgency and overflow urinary incontinence.

The Neighborhood Environment and Hispanic/Latino Health.

PURPOSE: Hispanic/Latino adults on the Texas-Mexico border have high rates of chronic disease. Neighborhoods can influence health, though there is a limited research on neighborhood environment and health in Hispanics/Latinos. The purpose of this study was to assess the relation of neighborhood environment with health variables in Hispanic/Latino adults, including physical activity [PA], depression, anxiety, and lab-assessed conditions (type 2 diabetes, metabolic syndrome, and chronic inflammation). METHODS: Participants were randomly-selected from a Hispanic/Latino cohort on the Texas-Mexico border. Neighborhood environment, self-reported PA, anxiety, and depression were assessed through questionnaires. Laboratory values determined Type 2 diabetes, metabolic syndrome, and C-reactive protein (CRP). We conducted multivariable linear and logistic regression analyses to assess the associations of neighborhood environment and health variables, controlling for covariates. RESULTS: Participants (n = 495) were mostly females, without insurance. After controlling for covariates, crime (Adjusted Odds Ratio [AOR] = 1.59 (95%CI 1.06-2.38), no streetlights (AOR = 1.65, 95%CI 1.06-2.57), and traffic (AOR = 1.74, 95%CI 1.16-2.62) were all significantly associated with anxiety. Only traffic was significantly associated with depression (AOR = 1.61, 95%CI1.05-2.47). A lack of nearby shops (AOR = 0.57, 95%CI 0.38-0.84) and no one out doing PA (AOR = 0.53, 95% CI 0.34-0.83) were both significantly associated with lower odds of meeting PA guidelines. A lack of nearby shops was associated with a 26% increase in the CRP value (ß = 0.26, 95%CI 0.04-0.47). DISCUSSION: Several neighborhood environment variables were significantly associated with mental health, PA and CRP, though estimates were small. The neighborhood environment is a meaningful contextual variable to consider for health-related interventions in Hispanic/Latino adults, though more study is needed regarding the magnitude of the estimates. TRIAL REGISTRATION: NCT01168765.

Association Between Body Fat Mass and Kidney Stones in US Adults: Analysis of the National Health and Nutrition Examination Survey 2011-2018.

BACKGROUND: The association between total and truncal body fat and kidney stone (KS) remains unclear. OBJECTIVE: To evaluate the association between total and truncal body fat and KS in the US adult population. DESIGN, SETTING, AND PARTICIPANTS: The National Health and Nutrition Examination Survey (NHANES) comprises a series of nationally representative cross-sectional surveys. Data from females and males aged 20-59 yr who participated in four 2-yr NHANES cycles between 2011 and 2018 were obtained. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariable-adjusted logistic regression models were used to investigate the association between dual-energy x-ray absorptiometry (DXA) scan-measured total and truncal body fat percentage and mass with KS. RESULTS AND LIMITATIONS: A total of 10 271 participants (50.3% females) were included. Weighted KS prevalence was 8.11% in femalesand 7.55% in males. In males, higher fat percentage was associated with higher odds of KS (per 5% total fat: odds ratio [OR] = 1.19, 95% confidence interval [CI] 1.08-1.32; per 5% truncal fat: OR = 1.22, 95% CI 1.10-1.35), particularly in those aged 40-59 yr (per 5% total fat: OR = 1.36, 95% CI 1.16-1.59; per 5% truncal fat: OR = 1.41, 95% CI 1.20-1.65, p-interaction < 0.05). In females, higher fat percentage was associated with higher odds of KS overall (per 5% total fat: OR = 1.23, 95% CI 1.10-1.37; per 5% truncal fat: OR = 1.20, 95% CI 1.08-1.33) and in both age groups (20-39 and 40-59 yr, p-interaction > 0.05). The observed associations were stronger in "other" ethnicities and non-Hispanic white. Similar patterns were observed for per 5 kg body fat mass. CONCLUSIONS: Total and truncal fat parameters are associated with a higher prevalence of KS in adult females and males who are ≥40 yr old. Truncal fat mass may be at least equal or superior to total fat mass in assessing the association of body fat with KS. Further studies are warranted to elaborate on the pathophysiologic mechanism of this association to decrease the prevalence of KS. PATIENT SUMMARY: Total and truncal body fat are associated with a higher prevalence of kidney stone (KS) in adult females and males aged ≥40 yr. Truncal fat mass may be similar or superior to total fat mass in assessing the association between body fat and KS.

Participant engagement in a community health worker-delivered intervention and type 2 diabetes clinical outcomes: a quasiexperimental study in MexicanAmericans.

OBJECTIVES: This study helps to fill the existing research gap related to participant engagement in behavioural interventions and diabetes management. We examined type 2 diabetes control over time among Mexican Americans by level of engagement in a chronic care management (CCM) program that included community health worker (CHW)-delivered multilevel interventions. The programme complemented clinical care and promoted behaviour changes to improve diabetes self-management. DESIGN: Quasiexperimental study. SETTING: The study was implemented in the Rio Grande Valley region in the USA. Recruitment was conducted in clinics and community events. All other visits were provided in participant homes and community locations. PARTICIPANTS: 5649 adults (aged ≥18 years) with poorly controlled type 2 diabetes who enrolled in a community-delivered CCM programme between September 2013 and 2018. INTERVENTIONS: The intervention comprised two components: CHW home visits conducted every 3 months and diabetes self-management education (DSME) classes provided in community locations. PRIMARY OUTCOME MEASURES: The primary outcome was haemoglobin A1c (HbA1c) measured at baseline every 3 months for up to 24 months. We first examined changes in HbA1c levels over time. The number of completed CHW and DSME encounters was used to classify participants into engagement groups-high engagement defined as ≥10 encounters (n=2952); low engagement defined as 1-9 encounters (n=2697). We used univariable and multivariable longitudinal linear regression models with a generalised estimating equation method. We tested interactions between engagement groups and time. RESULTS: Participants' mean HbA1c decreased from 10.20% at baseline to 8.93% (p<0.0001) at 3 months, remaining stable thereafter. Changes in HbA1c were statistically different between the engagement groups. High engagement participants had lower HbA1c levels over the first 15 months of the follow-up period compared with low engagement participants, as compared at 3 months (-0.44%, 95% CI -0.57% to -0.31%; p<0.0001), 6 months (-0.31%, 95% CI -0.43% to -0.14%; p<0.0001), 9 months (-0.27%, 95% CI -0.42% to -0.13%; p=0.0001), 12 months (-0.23%, 95% CI -0.37% to -0.08%; p=0.0025) and 15 months (-0.32%, 95% CI -0.54% to -0.10%; p=0.0040). At months 18, 21 and 24, the HbA1c differences were not statistically significant (18 months: -0.34%, 95% CI -0.77% to 0.08%; p=0.1086; 21 months: -0.22%, 95% CI -1.00% to 0.56%; p=0.5721; 24 months: -0.42%, 95% CI -1.38% to 0.55%; p=0.3966). CONCLUSIONS: Higher engagement in the CCM programme delivered by CHWs and coordinated with clinical care was associated with beneficial improvements in type 2 diabetes control, but both engagement groups showed strong improvements.

Coronary artery calcium score on standard of care oncologic CT scans for the prediction of adverse cardiovascular events in patients with non-small cell lung cancer treated with concurrent chemoradiotherapy.

Introduction: Chemoradiotherapy (CRT) has been associated with increased incidence of cardiovascular (CV) adverse events (CVAE). Coronary artery calcium scoring (CAC) has shown to predict coronary events beyond the traditional CV risk factors. This study examines whether CAC, measured on standard of care, non-contrast chest CT (NCCT) imaging, predicts the development of CVAE in patients with non-small cell lung cancer (NSCLC) treated with CRT. Methods: Patients with NSCLC treated with CRT at MD Anderson Cancer Center from 7/2009 until 4/2014 and who had at least one NCCT scan within 6 months from their first CRT were identified. CAC scoring was performed on NCCT scans by an expert cardiologist and a cardiac radiologist following the 2016 SCCT/STR guidelines. CVAE were graded based on the most recent Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. CVAE were also grouped into (i) coronary/vascular events, (ii) arrhythmias, or (iii) heart failure. All CVAE were adjudicated by a board-certified cardiologist. Results: Out of a total of 193 patients, 45% were female and 91% Caucasian. Mean age was 64 ± 9 years and mean BMI 28 ± 6 kg/m2. Of 193 patients, 74% had CAC >0 Agatston units (AU), 49% CAC ≥100 AU and 36% CAC ≥300 AU. Twenty-nine patients (15%) developed a grade ≥2 CVAE during a median follow-up of 24.3 months (IQR: 10.9-51.7). Of those, 11 (38%) were coronary/vascular events. In the multivariate cox regression analysis, controlling for mean heart dose and pre-existing CV disease, higher CAC score was independently associated with development of a grade ≥2 CVAE [HR: 1.04 (per 100 AU), 95% CI: 1.01-1.08, p = 0.022] and with worse overall survival (OS; CAC ≥100 vs. <100 AU, HR: 1.64, 95% CI: 1.11-2.44, p = 0.013). In a sub-analysis evaluating the type of the CVAE, it was the coronary/vascular events that were significantly associated with higher baseline CAC (median: 676 AU vs. 73 AU, p = 0.035). Discussion: Cardiovascular adverse events are frequent in patients with NSCLC treated with CRT. CAC calculated on "standard of care" NCCT can predict the development of CVAEs and specifically coronary/vascular events, as well as OS, independently from other traditional risk factors and radiation mean heart dose. Clinical trial registration: [https://clinicaltrials.gov/ct2/show/NCT00915005], identifier [NCT00915005].

Evaluating the Dissemination and Implementation of a Community Health Worker-Based Community Wide Campaign to Improve Fruit and Vegetable Intake and Physical Activity among Latinos along the U.S.-Mexico Border.

This study evaluated the dissemination and implementation of a culturally tailored community-wide campaign (CWC), Tu Salud ¡Si Cuenta! (TSSC), to augment fruit and vegetable (FV) consumption and physical activity (PA) engagement among low-income Latinos of Mexican descent living along the U.S.-Mexico Border in Texas. TSSC used longitudinal community health worker (CHW) home visits as a core vehicle to enact positive change across all socioecological levels to induce behavioral change. TSSC's reach, effectiveness, adoption, implementation, and maintenance (RE-AIM) was examined. A dietary questionnaire and the Godin-Shepherd Exercise Questionnaire measured program effectiveness on mean daily FV consumption and weekly PA engagement, respectively. Participants were classified based on CHW home visits into "low exposure" (2-3 visits) and "high exposure" (4-5 visits) groups. The TSSC program reached low-income Latinos (n = 5686) across twelve locations. TSSC demonstrated effectiveness as, compared to the low exposure group, the high exposure group had a greater FV intake (mean difference = +0.65 FV servings daily, 95% CI: 0.53-0.77) and an increased PA (mean difference = +185.6 MET-minutes weekly, 95% CI: 105.9-265.4) from baseline to the last follow-up on a multivariable linear regression analysis. Multivariable logistic regression revealed that the high exposure group had higher odds of meeting both FV guidelines (adjusted odds ratio (AOR) = 2.03, 95% CI: 1.65-2.47) and PA guidelines (AOR = 1.36, 95% CI: 1.10-1.68) at the last follow-up. The program had a 92.3% adoption rate, with 58.3% of adopting communities meeting implementation fidelity, and 91.7% of communities maintaining TSSC. TSSC improved FV consumption and PA engagement behaviors among low-income Latinos region wide. CHW delivery and implementation funding positively influenced reach, effectiveness, adoption, and maintenance, while lack of qualified CHWs negatively impacted fidelity.

Assessment of Prognostic Value of High-Sensitivity Cardiac Troponin T for Early Prediction of Chemoradiation Therapy-Induced Cardiotoxicity in Patients with Non-Small Cell Lung Cancer: A Secondary Analysis of a Prospective Randomized Trial.

PURPOSE: Cardiotoxicities induced by cancer therapy can negatively affect quality of life and survival. We investigated whether high-sensitivity cardiac troponin T (hs-cTnT) levels could serve as biomarker for early detection of cardiac adverse events (CAEs) after chemoradiation therapy (CRT) for non-small cell lung cancer (NSCLC). METHODS AND MATERIALS: This study included 225 patients who received concurrent platinum and taxane-doublet chemotherapy with thoracic radiation therapy to a total dose of 60 to 74 Gy for NSCLC. All patients were evaluated for CAEs; 190 patients also had serial hs-cTnT measurements. RESULTS: Grade ≥3 CAEs occurred in 24 patients (11%) at a median interval of 9 months after CRT. Pretreatment hs-cTnT levels were higher in men, in patients aged ≥64 years, and in patients with pre-existing heart disease or poor performance status (P < .05). hs-cTnT levels increased at 4 weeks during CRT (P < .05) and decreased after completion of CRT but did not return to pretreatment levels (P = .002). The change (Δ) in hs-cTnT levels during CRT correlated with mean heart dose (P = .0004), the heart volumes receiving 5 to 55 Gy (P < .05), and tumor location (P = .006). Risks of severe CAEs and mortality were significantly increased if the pretreatment hs-cTnT was >10 ng/L or the Δ during CRT was ≥5 ng/L. CONCLUSIONS: Elevation of hs-cTnT during CRT was radiation heart dose-dependent, and high hs-cTnT levels during the course of CRT were associated with CAEs and mortality. Routine monitoring of hs-cTnT could identify patients who are at high risk of CRT-induced CAEs early to guide modifications of cancer therapy and possible interventions to mitigate cardiotoxicity.

Scaling a Community-Wide Campaign Intervention to Manage Hypertension and Weight Loss.

Public health impacts can be achieved when evidence-based interventions are implemented to those most in need. Too often implementation never or slowly occurs. The community-wide campaign intervention Tu Salud ¡Si Cuenta! has evidence of improving health outcomes related to chronic disease among low-income, Latinos. Using the RE-AIM Framework, this study examined if the scaled-up version of the intervention is associated with improvements in hypertension and obesity in 12 locations. Each element of the RE-AIM framework was examined. For "Effectiveness," we examined outcomes overall and by implementing location. We used linear and logistic regression to assess if exposure in the intervention was associated with improvement in hypertension and weight loss. Participants were stratified into "low exposure" (2-3 outreach visits) vs. "high exposure" (4-5 outreach visits). Based on the RE-AIM Framework, the intervention "reached" its intended population of low-income Latinos, demonstrated "effectiveness" in improving hypertension and obesity, was "adopted" at a high level in all but one site, was "implemented" with fidelity to the intervention model with moderate success across locations, and showed high "maintenance" over time. For effectiveness specifically, we found that out of 5,019 participants, 2,508 (50%) had a baseline hypertensive blood pressure (BP) reading. Of the 2,508, 1,245 (49.9%) recovered to normal blood pressure or pre-hypertension stage by last follow-up. After adjusting for baseline BP and potential confounders in multivariable linear regression models, the high exposure group had significantly more reduction in systolic BP (adjusted mean difference in % change = -0.96; p = 0.002) and diastolic BP (adjusted mean difference in % change = -1.61; p < 0.0001) compared to the low exposure group. After controlling for baseline weight and other confounders, the high exposure group had significantly greater decrease in weight compared to the low exposure group (adjusted mean difference in % change = -1.28; p < 0.0001). Results from the multivariable logistic regression models indicated that compared to the low exposure group the high exposure group was more likely to achieve a clinically significant minimum 5% weight loss [adjusted odds ratio (OR) = 2.97; p < 0.0001). This study contributes evidence that a Community-Wide Campaign model holds promise for addressing hypertension and obesity among low-income Latinos.

Prevalence and Trends in Kidney Stone Among Adults in the USA: Analyses of National Health and Nutrition Examination Survey 2007-2018 Data.

BACKGROUND: The contemporary prevalence and trends of kidney stones are not clear. OBJECTIVE: To evaluate the gender-specific prevalence and trends in kidney stones among the US population. DESIGN, SETTING, AND PARTICIPANTS: Data on self-reported history of kidney stones from 34 749 participants aged ≥20 yr from the National Health and Nutrition Examination Survey (NHANES) were analyzed. INTERVENTION: Six 2-yr study cycles (2007-2008 to 2017-2018) of nationally representative series of surveys evaluated the health status of the US population. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Weighted prevalence estimates of kidney stones and 95% confidence intervals (CIs) were calculated in each study cycle. Multivariable-adjusted logistic regression models were used to investigate the temporal trends. RESULTS AND LIMITATIONS: In the 2017-2018 cycle, the prevalence of kidney stones was 10.9% (CI: 9.3-12.7) in men as compared with 9.5% (CI: 8-11.2) in women. The prevalence of kidney stones increased steadily from 6.5% in the 2007-2008 cycle to 9.4% in the 2017-2018 cycle (ptrend = 0.001) among women but not among men (ptrend = 0.1). These trends remained after adjusting for sociodemographic correlates in both genders. Sensitivity analyses further adjusting for dietary information held the same results in trends (men: ptrend = 0.15; women: ptrend = 0.001). Non-Hispanic white ethnicity, obesity, gout, history of two or more pregnancies, menopause, and using female hormones were associated with a higher prevalence of kidney stones. The main limitation is the cross-sectional design of the study. CONCLUSIONS: Although kidney stones are more common in men than in women in the USA, the gender gap in kidney stone prevalence appears to be closing in the past decade. Kidney stones are consistently higher among non-Hispanic white and obese, and women who have had multiple pregnancies or have used female hormone therapy. PATIENT SUMMARY: The prevalence of kidney stones remains higher in adult US men than in women, but the trend has been increasing only in women, closing the gender gap in kidney stone prevalence.

Identification of Novel Carbocyclic Pyrimidine Cyclic Dinucleotide STING Agonists for Antitumor Immunotherapy Using Systemic Intravenous Route.

Stimulator of Interferon Genes (STING) plays an important role in innate immunity by inducing type I interferon production upon infection with intracellular pathogens. STING activation can promote increased T-cell activation and inflammation in the tumor microenvironment, resulting in antitumor immunity. Natural and synthetic cyclic dinucleotides (CDNs) are known to activate STING, and several synthetic CDN molecules are being investigated in the clinic using an intratumoral administration route. Here, we describe the identification of STING agonist 15a, a cyclic dinucleotide structurally diversified from natural ligands with optimized properties for systemic intravenous (iv) administration. Our studies have shown that STING activation by 15a leads to an acute innate immune response as measured by cytokine secretion and adaptive immune response via activation of CD8+ cytotoxic T-cells, which ultimately provides robust antitumor efficacy.