Reconsidering stepped wedge cluster randomized trial designs with implementation periods: Fewer sequences or the parallel-group design with baseline and implementation periods are potentially more efficient.

BACKGROUND/AIMS: When designing a cluster randomized trial, advantages and disadvantages of tentative designs must be weighed. The stepped wedge design is popular for multiple reasons, including its potential to increase power via improved efficiency relative to a parallel-group design. In many realistic settings, it will take time for clusters to fully implement the intervention. When designing the HEALing (Helping to End Addiction Long-termSM) Communities Study, implementation time was a major consideration, and we examined the efficiency and practicality of three designs. Specifically, a three-sequence stepped wedge design with implementation periods, a corresponding two-sequence modified design that is created by removing the middle sequence, and a parallel-group design with baseline and implementation periods. In this article, we study the relative efficiencies of these specific designs. More generally, we study the relative efficiencies of modified designs when the stepped wedge design with implementation periods has three or more sequences. We also consider different correlation structures. METHODS: We compare efficiencies of stepped wedge designs with implementation periods consisting of three to nine sequences with a variety of corresponding designs. The three-sequence design is compared to the two-sequence modified design and to the parallel-group design with baseline and implementation periods analysed via analysis of covariance. Stepped wedge designs with implementation periods consisting of four or more sequences are compared to modified designs that remove all or a subset of 'middle' sequences. Efficiencies are based on the use of linear mixed effects models. RESULTS: In the studied settings, the modified design is more efficient than the three-sequence stepped wedge design with implementation periods. The parallel-group design with baseline and implementation periods with analysis of covariance-based analysis is often more efficient than the three-sequence design. With respect to stepped wedge designs with implementation periods that are comprised of more sequences, there are often corresponding modified designs that improve efficiency. However, use of only the first and last sequences has the potential to be either relatively efficient or inefficient. Relative efficiency is impacted by the strength of the statistical correlation among outcomes from the same cluster; for example, the relative efficiencies of modified designs tend to be greater for smaller cluster auto-correlation values. CONCLUSION: If a three-sequence stepped wedge design with implementation periods is being considered for a future cluster randomized trial, then a corresponding modified design using only the first and last sequences should be considered if sole focus is on efficiency. However, a parallel-group design with baseline and implementation periods and analysis of covariance-based analysis can be a practical, efficient alternative. For stepped wedge designs with implementation periods and a larger number of sequences, modified versions that remove 'middle' sequences should be considered. Due to the potential sensitivity of design efficiencies, statistical correlation should be carefully considered.

Entospletinib with decitabine in acute myeloid leukemia with mutant TP53 or complex karyotype: A phase 2 substudy of the Beat AML Master Trial.

BACKGROUND: Patients with acute myeloid leukemia (AML) who have tumor protein p53 (TP53) mutations or a complex karyotype have a poor prognosis, and hypomethylating agents are often used. The authors evaluated the efficacy of entospletinib, an oral inhibitor of spleen tyrosine kinase, combined with decitabine in this patient population. METHODS: This was a multicenter, open-label, phase 2 substudy of the Beat AML Master Trial (ClinicalTrials.gov identifier NCT03013998) using a Simon two-stage design. Eligible patients aged 60 years or older who had newly diagnosed AML with mutations in TP53 with or without a complex karyotype (cohort A; n = 45) or had a complex karyotype without TP53 mutation (cohort B; n = 13) received entospletinib 400 mg twice daily with decitabine 20 mg/m2 on days 1-10 every 28 days for up to three induction cycles, followed by up to 11 consolidation cycles, in which decitabine was reduced to days 1-5. Entospletinib maintenance was given for up to 2 years. The primary end point was complete remission (CR) and CR with hematologic improvement by up to six cycles of therapy. RESULTS: The composite CR rates for cohorts A and B were 13.3% (95% confidence interval, 5.1%-26.8%) and 30.8% (95% confidence interval, 9.1%-61.4%), respectively. The median duration of response was 7.6 and 8.2 months, respectively, and the median overall survival was 6.5 and 11.5 months, respectively. The study was stopped because the futility boundary was crossed in both cohorts. CONCLUSIONS: The combination of entospletinib and decitabine demonstrated activity and was acceptably tolerated in this patient population; however, the CR rates were low, and overall survival was short. Novel treatment strategies for older patients with TP53 mutations and complex karyotype remain an urgent need.

Differences in obesity-related health behaviors and health outcomes by rural and Appalachian residency.

PURPOSE: Obesity and health behaviors are the major modifiable contributors to cancer and health disparities. We examined the differences in obesity-related health behaviors, and health outcomes by rural and Appalachian residency in Ohio. METHODS: Cross-sectional survey data from the 2011-2019 Behavioral Risk Factor Surveillance System were obtained from the Ohio Department of Health. County-level identifiers were used to classify urban non-Appalachian, urban Appalachian, rural non-Appalachian, and rural Appalachian residency. Self-reported weight, height, health behaviors, and health conditions were used. Logistic regression was used to assess the difference in health behaviors and health outcomes by rural and Appalachian residency. All analyses incorporated with sample weights. RESULTS: Among Ohio residents, compared to urban non-Appalachian residents, urban Appalachian and rural Appalachian residents had a higher prevalence of obesity, hypertension, high cholesterol, and cardiovascular diseases, as well as lower rates of healthy diet and physical activity. No difference was found in trends of obesity and obesity-related health outcomes in 2011-2019 by rural and Appalachian residency. However, rural Appalachian residents had a greater increase in obesity, hypertension, and diabetes, whereas rural non-Appalachian had favorable changes in obesity-related health behaviors. Additionally, associations between health behaviors and obesity-related health outcomes differed by rural and Appalachian residency. CONCLUSIONS: Findings underscore the importance of distinguishing between urban non-Appalachian, urban Appalachian, rural non-Appalachian, and rural Appalachian populations when assessing health disparities. While the trends of obesity and obesity-related health outcomes did not differ, the association between health behaviors and obesity-related outcomes differed by rural and Appalachian residency.

BRCAShare-Assessment of an animated digital message for intrafamilial communication of pathogenic variant positive test results: A feasibility study.

While genetic testing for hereditary breast and ovarian cancer syndrome (HBOC) is well-established in the field of medicine, family members' uptake of cascade genetic testing for known familial pathogenic variants remains low. Probands often become responsible for initiating familial communication about their testing results, and barriers to communication may include difficulty in conveying information to relatives and a lack of communication resources for probands' use. In this study, we tested a two-minute animated digital message (ADM) intervention guided by the Health Belief Model (HBM) in an unselected sample to determine hypothetical individual perceptions of susceptibility and severity and behavioral intention to act on the information provided in the ADM. We recruited genetic testing naïve adults from the United States with no personal history of cancer through Amazon Mechanical Turk to participate in this study. Participants were presented a hypothetical scenario describing a relative's recent HBOC diagnosis, viewed the ADM, and answered a questionnaire assessing participants' perception of the HBM constructs in relation to the hypothetical scenario and participants' intentions to pursue cascade genetic testing, talk to a healthcare professional, or talk to family members after ADM viewing. Participants (n = 373) largely perceived HBOC as serious and believed that they could benefit from the information provided by genetic testing; 76% hypothetically intended to pursue genetic testing at a cost of $100 or less, and 90% intended to either pursue testing or talk to a healthcare provider or family members. This feasibility study in an unaffected population could mimic the experience of distant/less-engaged relatives in HBOC families after receiving unexpected information about cascade genetic testing. Most participants demonstrated behavioral intention toward cascade testing, at a rate higher than literature would suggest is typical in high-risk families, indicating that a theory-supported, simple to use intervention may be useful in clinical practice.

Predictors of Stress Exposure in Hospitalized Preterm Infants.

BACKGROUND: Stress exposure in the neonatal intensive care unit (NICU) is associated with poor outcomes in preterm infants. However, factors predicting subsequent NICU stress exposure have not been identified. PURPOSE: To characterize NICU stressors experienced by preterm infants during the first 2 weeks of life and identify demographic, perinatal, and institutional variables associated with stress exposure. METHODS: A secondary analysis of data from a nonexperimental, prospective study was conducted using data from 60 very preterm infants born 28 to 31 weeks gestational age. Stress exposures during the first 2 weeks of life, operationalized as number of invasive procedures, were characterized by type and quantity for each infant using data extracted from electronic health records. Associations between number of invasive procedures and demographic, perinatal, or institutional variables were analyzed using linear regressions with robust standard errors. RESULTS: Preterm infants experienced, on average, 98 (SD = 41.8) invasive procedures. Of these invasive procedures, nasal and/or oral suctioning episodes (58.1%), followed by skin-breaking procedures (32.6%), were most frequent. Differences in the number of invasive procedures were found for maternal race; infants born to Black mothers experienced fewer total invasive procedures than infants born to White mothers. The number of invasive procedures also varied across NICUs. IMPLICATIONS FOR PRACTICE AND RESEARCH: Preterm infant stress exposure differed by maternal race and NICU, consistent with research findings of differential treatment of diverse infants. Further research is needed to understand the reasons for these differences and to identify best practices to standardize neonatal care.

The Role of Cigarillo Flavor in the Co-Use of Cigarillos and Cannabis among Young Adults.

Background: Research suggests flavor facilitates cigarillo use, but it is unknown if flavor impacts patterns of co-use of cigarillos and cannabis ("co-use"), which is common among young adult smokers. This study's aim was to determine the role of the cigarillo flavor in co-use among young adults. Methods: Data were collected (2020-2021) in a cross-sectional online survey administered to young adults who smoked ≥2 cigarillos/week (N = 361), recruited from 15 urban areas in the United States. A structural equation model was used to assess the relationship between flavored cigarillo use and past 30-day cannabis use (flavored cigarillo perceived appeal and harm as parallel mediators), including several social-contextual covariates (e.g., flavor and cannabis policies). Results: Most participants reported usually using flavored cigarillos (81.8%) and cannabis use in the past 30 days ("co-use") (64.1%). Flavored cigarillo use was not directly associated with co-use (p = 0.90). Perceived cigarillo harm (ß = 0.18, 95% CI = 0.06, 0.29), number of tobacco users in the household (ß = 0.22, 95% CI = 0.10, 0.33), and past 30-day use of other tobacco products (ß = 0.23, 95% CI = 0.15, 0.32) were significantly positively associated with co-use. Living in an area with a ban on flavored cigarillos was significantly negatively associated with co-use (ß = -0.12, 95% CI = -0.21, -0.02). Conclusions: Use of flavored cigarillos was not associated with co-use; however, exposure to a flavored cigarillo ban was negatively associated with co-use. Cigar product flavor bans may reduce co-use among young adults or have a neutral impact. Further research is needed to explore the interaction between tobacco and cannabis policy and use of these products.

Marginal modeling in community randomized trials with rare events: Utilization of the negative binomial regression model.

BACKGROUND/AIMS: This work is motivated by the HEALing Communities Study, which is a post-test only cluster randomized trial in which communities are randomized to two different trial arms. The primary interest is in reducing opioid overdose fatalities, which will be collected as a count outcome at the community level. Communities range in size from thousands to over one million residents, and fatalities are expected to be rare. Traditional marginal modeling approaches in the cluster randomized trial literature include the use of generalized estimating equations with an exchangeable correlation structure when utilizing subject-level data, or analogously quasi-likelihood based on an over-dispersed binomial variance when utilizing community-level data. These approaches account for and estimate the intra-cluster correlation coefficient, which should be provided in the results from a cluster randomized trial. Alternatively, the coefficient of variation or R coefficient could be reported. In this article, we show that negative binomial regression can also be utilized when communities are large and events are rare. The objectives of this article are (1) to show that the negative binomial regression approach targets the same marginal regression parameter(s) as an over-dispersed binomial model and to explain why the estimates may differ; (2) to derive formulas relating the negative binomial overdispersion parameter k with the intra-cluster correlation coefficient, coefficient of variation, and R coefficient; and (3) analyze pre-intervention data from the HEALing Communities Study to demonstrate and contrast models and to show how to report the intra-cluster correlation coefficient, coefficient of variation, and R coefficient when utilizing negative binomial regression. METHODS: Negative binomial and over-dispersed binomial regression modeling are contrasted in terms of model setup, regression parameter estimation, and formulation of the overdispersion parameter. Three specific models are used to illustrate concepts and address the third objective. RESULTS: The negative binomial regression approach targets the same marginal regression parameter(s) as an over-dispersed binomial model, although estimates may differ. Practical differences arise in regard to how overdispersion, and hence the intra-cluster correlation coefficient is modeled. The negative binomial overdispersion parameter is approximately equal to the ratio of the intra-cluster correlation coefficient and marginal probability, the square of the coefficient of variation, and the R coefficient minus 1. As a result, estimates corresponding to all four of these different types of overdispersion parameterizations can be reported when utilizing negative binomial regression. CONCLUSION: Negative binomial regression provides a valid, practical, alternative approach to the analysis of count data, and corresponding reporting of overdispersion parameters, from community randomized trials in which communities are large and events are rare.

The impact of a cascade testing video on recipients' knowledge, cognitive message processing, and affective reactions: A formative evaluation.

Cascade genetic testing is essential to clarify cancer risk in families with hereditary breast and ovarian cancer syndrome (HBOC) due to pathogenic variants (PVs) in BRCA1 or BRCA2. To date, data suggest that family communication of genetic testing results, with or without the aid of clinical resources such as a provider-written family letter, is impacted by multiple barriers. These barriers eventually lead to sub-optimal uptake of cascade genetic testing. We designed a 2-min animated video that a proband can share with relatives to notify them that the proband has tested positive for a pathogenic variant in BRCA1 or BRCA2. We studied the video via hypothetical scenario in an unselected population to simulate the process by which a relative receives unsolicited genetics information about their family member. We assessed the impact of the video on three specific domains: knowledge, cognitive message processing, and affective reactions. A total of 399 participants recruited through Amazon Mechanical Turk completed the study, and 373 were analyzed. The video significantly improved content knowledge/recall (p < .0001) from pre- to post-video viewing, indicating effective message communication. Items used to measure cognitive processing showed preliminary tendencies toward systematic message processing, which could be desired in familial communication aimed at initiating a specific action-in this case, cascade genetic testing. A majority of participants (66%) reported positive affective reaction as they indicated that they would feel gratitude if they received the video message from a relative, and did not evidence a negative affective reaction to receiving the information. Our data suggest that a video message can effectively communicate information about cascade genetic testing to potential relatives with as little as two minutes of content. Our data suggest that video messaging to assist family communication is a reasonable approach that increases understanding and is unlikely to cause harm.

Multiple imputation by predictive mean matching in cluster-randomized trials.

BACKGROUND: Random effects regression imputation has been recommended for multiple imputation (MI) in cluster randomized trials (CRTs) because it is congenial to analyses that use random effects regression. This method relies heavily on model assumptions and may not be robust to misspecification of the imputation model. MI by predictive mean matching (PMM) is a semiparametric alternative, but current software for multilevel data relies on imputation models that ignore clustering or use fixed effects for clusters. When used directly for imputation, these two models result in underestimation (ignoring clustering) or overestimation (fixed effects for clusters) of variance estimates. METHODS: We develop MI procedures based on PMM that leverage these opposing estimated biases in the variance estimates in one of three ways: weighting the distance metric (PMM-dist), weighting the average of the final imputed values from two PMM procedures (PMM-avg), or performing a weighted draw from the final imputed values from the two PMM procedures (PMM-draw). We use Monte-Carlo simulations to evaluate our newly proposed methods relative to established MI procedures, focusing on estimation of treatment group means and their variances after MI. RESULTS: The proposed PMM procedures reduce the bias in the MI variance estimator relative to established methods when the imputation model is correctly specified, and are generally more robust to model misspecification than even the random effects imputation methods. CONCLUSIONS: The PMM-draw procedure in particular is a promising method for multiply imputing missing data from CRTs that can be readily implemented in existing statistical software.

Information growth for sequential monitoring of clinical trials with a stepped wedge cluster randomized design and unknown intracluster correlation.

BACKGROUND/AIMS: In a stepped wedge study design, study clusters usually start with the baseline treatment and then cross over to the intervention at randomly determined times. Such designs are useful when the intervention must be delivered at the cluster level and are becoming increasingly common in practice. In these trials, if the outcome is death or serious morbidity, one may have an ethical imperative to monitor the trial and stop before maximum enrollment if the new therapy is proven to be beneficial. In addition, because formal monitoring allows for the stoppage of trials when a significant benefit for new therapy has been ruled out, their use can make a research program more efficient. However, use of the stepped wedge cluster randomized study design complicates the implementation of standard group sequential monitoring methods. Both the correlation of observations introduced by the clustered randomization and the timing of crossover from one treatment to the other impact the rate of information growth, an important component of an interim analysis. METHODS: We simulated cross-sectional stepped wedge study data in order to evaluate the impact of sequential monitoring on the Type I error and power when the true intracluster correlation is unknown. We studied the impact of varying intracluster correlations, treatment effects, methods of estimating the information growth, and boundary shapes. RESULTS: While misspecified information growth can impact both the Type I error and power of a study in some settings, we observed little inflation of the Type I error and only moderate reductions in power across a range of misspecified information growth patterns in our simulations. CONCLUSION: Taking the study design into account and using either an estimate of the intracluster correlation from the ongoing study or other data in the same clusters should allow for easy implementation of group sequential methods in future stepped wedge designs.

Measures of Stress Exposure for Hospitalized Preterm Infants.

BACKGROUND: Extended hospitalization in neonatal intensive care units subjects preterm infants to multiple stress exposures that affect long-term cognitive functioning, motor development, and stress reactivity. Measurement of stress exposure is challenging with multiple measures of stress exposure in use, including counts of skin-breaking or invasive procedures or counts of noxious sensory exposures. OBJECTIVES: The purpose of this analysis was to compare measures of stress exposure commonly used by researchers and to determine the predictive validity of these measures for early neurobehavior. We accomplished this objective through the following specific aims: (a) describe the stress exposures of preterm infants in the first 2 weeks of life, (b) determine the correlations among measures of stress exposure, and (c) compare the predictive validity of measures of stress exposure for early neurobehavior. METHODS: Very preterm infants born between 28 and 31 weeks postmenstrual age were enrolled from four neonatal intensive care units in a large Midwest city. We measured stress exposure over the first 14 days of life for each infant as a count of skin-breaking procedures, a count of invasive procedures, and cumulative scores derived from the Neonatal Infant Stressor Scale. Neurobehavior was assessed at 35 weeks postmenstrual age using the motor development and vigor and alertness/orientation subscales from the Neurobehavioral Assessment of the Preterm Infant. We used Spearman's rho to determine correlations among the measures of stress exposure and multiple linear regression to determine the predictive validity of each stress exposure measure for neurobehavioral outcomes. RESULTS: Seventy-one preterm infants were included in the analysis. We found marked variance across individuals in all measures of stress exposure. There were moderate-high correlations among the measures of stress exposure. No measure of stress exposure was associated with early neurobehavior. DISCUSSION: The stress experiences of hospitalized preterm infants vary. This variance is reflected in all measures of stress exposure. Because measures of stress exposure are highly correlated, the most objective measure requiring the least interpretation should be used. However, the currently available measures of stress exposure used in this analysis may not reflect the infant's physiological stress responses and fail to associate with early neurobehavior.

Early Inflammatory Measures and Neurodevelopmental Outcomes in Preterm Infants.

BACKGROUND: Inflammation may be an important predictor of long-term neurodevelopment in preterm infants. The identification of specific inflammatory biomarkers that predict outcomes is an important research goal. OBJECTIVES: The purpose of this analysis was to identify associations between an early measure of inflammation and neurodevelopment in very preterm infants and to identify differences in the relationship between inflammation and neurodevelopment based on infant gender and race. METHODS: We conducted a secondary analysis of data from a randomized controlled trial of a caregiving intervention for preterm infants born less than 33 weeks postmenstrual age. Plasma was collected with a clinically indicated laboratory draw by neonatal intensive care unit nurses and analyzed by multiplex assay for cytokines, chemokines, and growth factors. Neurobehavior was assessed by research nurses at the time of discharge from the neonatal intensive care unit using the motor development and vigor and alertness/orientation clusters from the Neurobehavioral Assessment of the Preterm Infant. Neurodevelopment was assessed at 6 months corrected age by the developmental specialist in the hospital's neonatal follow-up clinic using the Bayley Scales of Infant Development, Third Edition. We used linear regressions to estimate the effect of cytokine levels on neurodevelopment and allowed the effects to differ by infant gender and race. RESULTS: In a sample of 62 preterm infants with discharge neurobehavioral assessments and a sample of 40 preterm infants with 6-month neurodevelopmental assessments, we found inconsistent associations between single-time point inflammatory measures and neurobehavior or neurodevelopment in analyses of the total sample. However, regressions with interactions revealed effects for multiple inflammatory measures on early neurobehavior and neurodevelopment that differed by infant gender and race. DISCUSSION: Although early single-time point measures of inflammation may be insufficient to predict neurodevelopment for all preterm infants, the effect of inflammation appears to differ by infant gender and race. These demographic factors may be important considerations for future studies of inflammation and neurodevelopment as well was the development of future interventions to optimize outcomes.

Statin users have an elevated risk of dysglycemia and new-onset-diabetes.

OBJECTIVE: Statins are one of the most widely prescribed medications in the United States; however, there is a concern that they are associated with new-onset-diabetes (NOD) development. We sought to understand the risk of dysglycemia and NOD for a cohort of individuals that reflect real-world physician prescribing patterns. METHODS: A retrospective cohort study was conducted among individuals with indications for statin use (n = 7064). To examine elevated glycosylated hemoglobin (>6.0%), logistic regression with inverse probability weighting was used to create balance between incident statin users and nonusers. To evaluate the risk of NOD development, Cox PH models with time varying statin use compared NOD diagnoses among statin users and nonusers. RESULTS: A higher prevalence of elevated HbA1c (PD = 0.065; 95% CI: 0.002, 0.129, P = 0.045) occurred among nondiabetic incident users of statins. Additionally, statin users had a higher risk of developing NOD (AHR = 2.20; 95% CI: 1.35, 3.58, P = 0.002). Those taking statins for 2 years or longer (AHR = 3.33; 95% CI: 1.84, 6.01, P < 0.001) were at the greatest risk of developing NOD; no differences were observed by statin class or intensity of dose. CONCLUSION: As lifestyle programs like the Diabetes Prevention Program are promoted in primary care settings, we hope physicians will integrate and insurers support healthy lifestyle strategies as part of the optimal management of individuals at risk for both NOD and cardiovascular disease. The relationships between statin use and glycemic control should be evaluated in large cohort studies, medical record databases, and mechanistic investigations to inform clinical judgment and treatment.

Results of a Pilot Study of a Mail-Based Human Papillomavirus Self-Testing Program for Underscreened Women From Appalachian Ohio.

BACKGROUND: Human papillomavirus (HPV) self-testing is an emerging cervical cancer screening strategy, yet few mail-based HPV self-testing programs have been implemented in the United States. We report the results of a pilot study of a mail-based program, the Health Outcomes through Motivation and Education Project. METHODS: In 2015 to 2016, we recruited 103 women from Appalachian Ohio who were aged 30 to 65 years and had not received a Papanicolaou (Pap) test in at least 3 years. Women were mailed an HPV self-test and randomized to receive either (a) self-test instructions developed by the device manufacturer and a standard information brochure about cervical cancer (control group) or (b) self-test instructions developed by the Health Outcomes through Motivation and Education Project and a photo story information brochure about cervical cancer (intervention group). Logistic regression compared study arms on HPV self-test return and receipt of a Pap test. RESULTS: Overall, 80 (78%) women returned their HPV self-test. Return was similar among the intervention and control groups (78% vs. 77%; odds ratio, 1.09; 95% confidence interval, 0.43-2.76). Among returners, 26% had an oncogenic HPV type detected in their sample. Women who returned their self-test reported high levels of satisfaction and positive experiences with the self-testing process. Few women overall received a Pap test (11%), and Pap testing was similar among the intervention and control groups (14% vs. 8%; odds ratio, 1.91; 95% confidence interval, 0.52-6.97). CONCLUSIONS: Mail-based HPV self-testing programs are a potentially promising strategy for reaching underscreened women in Appalachia. Efforts are needed to better understand how to optimize the success of such programs.

The Influence of Health Numeracy and Health Warning Label Type on Smoking Myths and Quit-Related Reactions.

INTRODUCTION: Health numeracy helps individuals understand risk information, but limited data exist concerning numeracy's role in reactions to varying types of health warning labels (HWLs) for cigarettes. METHODS: A nationally representative online panel of adult current smokers received two exposures (1 week apart) to nine HWLs with either text-only or pictorial images with identical mandated text. Following the second exposure, participants (n = 594) rated their beliefs in smoking myths (eg, health-promoting behaviors can undo the risks of smoking) and how much the warnings made them want to quit smoking. Generalized estimating equation regression examined the relation of objective health numeracy and its interaction with HWL type to smoking-myth beliefs and quit-related reactions. RESULTS: Health numeracy was not significantly associated with smoking-myth beliefs; the interaction with HWL type was also nonsignificant. Adult smokers with lower health numeracy had higher quit-related reactions than those with higher numeracy following exposure to HWLs. The type of HWL significantly modified numeracy's associations with quit-related reactions; no significant association existed between text-only HWLs and quit-related reactions, whereas among those who viewed the pictorial warnings, lower numeracy was associated with greater quit-related reactions (ß = -.23; p < .001). CONCLUSIONS: Lower as compared to higher health numeracy was significantly associated with higher quit-related reactions to HWLs and especially with pictorial HWLs. Health numeracy and HWL type were not associated with the endorsement of smoking myths. The role of health numeracy in effectively communicating risks to smokers warrants thoughtful consideration in the development of tobacco HWLs. IMPLICATIONS: Health numeracy plays an important role in an individual's ability to understand and respond to health risks. Smokers with lower health numeracy had greater quit-related reactions to pictorial health warnings than those who viewed text-only warning labels. Development and testing of health warning labels should consider health numeracy to most effectively communicate risk to US smokers.

Inflammatory mediators of stress exposure and neurodevelopment in very preterm infants: Protocol for the stress neuro-immune study.

AIMS: (a) Determine relationships among stress exposure, inflammation, and neurodevelopment in very preterm infants and determine the mediated effect of inflammation on the relationship between stress exposure and neurodevelopment; (b) describe cytokine trajectories following birth and determine the effect of stress exposure on these trajectories; and (c) examine relationships between stress exposure and chronic stress responses in very preterm infants. DESIGN: Non-experimental, repeated measures. METHODS: Very preterm infants born 28-31 weeks post menstrual age will be enrolled. Cumulative stress exposure over the first 14 days of life will be measured using the Neonatal Infant Stressor Scale. Blood will be collected weekly for the quantification of cytokines. Neurodevelopment will be assessed using the Neurobehavioral Assessment of the Preterm Infant and hair for quantification of hair cortisol will be collected at 35 weeks post menstrual age. Multiple linear regression and conditional process analysis will be used to analyse the relationships among stress exposure, inflammation and neurodevelopment. Linear mixed models will be used to determine inflammatory trajectories over time. IRB approval for the study was received May 2017, and funding from the National Institute of Nursing Research was awarded July 2017. DISCUSSION: This study will determine the extent to which inflammation mediates the relationship between stress exposure and neurodevelopment. Interventions to attenuate inflammation in preterm infants may improve outcomes. IMPACT: Determining the potentially modifiable mediators of stress exposure and neurodevelopment in preterm infants is critical to improving long-term outcomes.

Progression of care among women who use a midwife for prenatal care: Who remains in midwife care?

BACKGROUND: Prenatal care provided by midwives provides a safe and cost-effective alternative to care provided by physicians. However, no studies have evaluated the frequency of women who leave midwifery care, in a hospital setting. Our study objectives were to measure the frequency of transfers of care to physicians, to describe the sociodemographic and pregnancy-related characteristics of women who transferred to the care of a physician during prenatal care and at delivery, and to assess correlates of these transfers. METHODS: We used electronic medical records to perform a retrospective cohort study of women who delivered at The Ohio State University Wexner Medical Center (OSUWMC) and had at least one prenatal care visit within OSUWMC's network. We report descriptive findings, using proportions and means with standard deviations. We used logistic regression, with Firth's bias correction as necessary, to assess correlates of transferring to a physician during prenatal care and at delivery. RESULTS: Most women who initiated prenatal care with a midwife remained in midwifery care throughout delivery, with 4.7% transferring to a physician during prenatal care, and an additional 21.4% transferring to a physician during delivery. After adjusting for pregnancy-related factors, the black race was statistically significantly associated with leaving midwifery care during prenatal care (adjusted odds ratio AOR 3.0 [95% CI 1.4-6.6]) and delivery (AOR 2.5 [95% CI 1.5-4.3]). CONCLUSION: Findings indicate that most women remain in midwifery care throughout pregnancy, but raise important questions with respect to the possible role that race has in pregnancy care.

Effects of an Education Intervention about HPV Self-Testing for Healthcare Providers and Staff.

Human papillomavirus (HPV) self-testing is an emerging cervical cancer screening strategy, yet efforts to educate healthcare providers and staff about HPV self-testing are lacking. We report the findings of a brief education intervention about HPV self-testing for healthcare providers and staff. We conducted education sessions during 2015 with healthcare providers and staff (n = 33) from five federally qualified health centers located in Appalachian Ohio. Participants attended a one-time session and completed pre- and post-intervention surveys. Analyses for paired data assessed changes in knowledge and beliefs about HPV, HPV-related disease, and HPV self-testing. The intervention increased participants' knowledge and affected many of the beliefs examined. Participants answered an average of 4.67 of six knowledge items correctly on pre-intervention surveys and 5.82 items correctly on post-intervention surveys (p < 0.001). The proportion of participants who answered all six knowledge items correctly increased substantially (pre-intervention =9% vs. post-intervention =82%, p < 0.001). Compared to pre-intervention surveys, participants more strongly believed on post-intervention surveys that it is important to examine HPV self-testing as a potential cervical cancer screening strategy, that their female patients would be willing to use an HPV self-test at home by themselves, and that they have the knowledge to talk with their patients about HPV self-testing (all p < 0.05). A brief education intervention can be a viable approach for increasing knowledge and affecting beliefs about HPV self-testing among healthcare providers and staff. Findings will be valuable for planning and developing future HPV self-test interventions that include an education component for healthcare providers and staff.

Cigarette Graphic Warning Labels Are Not Created Equal: They Can Increase or Decrease Smokers' Quit Intentions Relative to Text-Only Warnings.

INTRODUCTION: Cigarette graphic-warning labels elicit negative emotion. Research suggests negative emotion drives greater risk perceptions and quit intentions through multiple processes. The present research compares text-only warning effectiveness to that of graphic warnings eliciting more or less negative emotion. METHODS: Nationally representative online panels of 736 adult smokers and 469 teen smokers/vulnerable smokers were randomly assigned to view one of three warning types (text-only, text with low-emotion images, or text with high-emotion images) four times over 2 weeks. Participants recorded their emotional reaction to the warnings (measured as arousal), smoking risk perceptions, and quit intentions. Primary analyses used structural equation modeling. RESULTS: Participants in the high-emotion condition reported greater emotional reaction than text-only participants (bAdult = 0.21; bTeen = 0.27, p's < .004); those in the low-emotion condition reported lower emotional reaction than text-only participants (bAdult = -0.18; bTeen = -0.22, p's < .018). Stronger emotional reaction was associated with increased risk perceptions in both samples (bAdult = 0.66; bTeen = 0.85, p's < .001) and greater quit intentions among adults (bAdult = 1.00, p < .001). Compared to text-only warnings, low-emotion warnings were associated with reduced risk perceptions and quit intentions whereas high-emotion warnings were associated with increased risk perceptions and quit intentions. CONCLUSION: Warning labels with images that elicit more negative emotional reaction are associated with increased risk perceptions and quit intentions in adults and teens relative to text-only warnings. However, graphic warnings containing images which evoke little emotional reaction can backfire and reduce risk perceptions and quit intentions versus text-only warnings. IMPLICATIONS: This research is the first to directly manipulate two emotion levels in sets of nine cigarette graphic warning images and compare them with text-only warnings. Among adult and teen smokers, high-emotion graphic warnings were associated with increased risk perceptions and quit intentions versus text-only warnings. Low-emotion graphic warnings backfired and tended to reduce risk perceptions and quit intentions versus text-only warnings. Policy makers should be aware that merely placing images on cigarette packaging is insufficient to increase smokers' risk perceptions and quit intentions. Low-emotion graphic warnings will not necessarily produce desired population-level benefits relative to text-only or high-emotion warnings.

Health Warning Labels for Smokeless Tobacco: The Impact of Graphic Images on Attention, Recall, and Craving.

INTRODUCTION: Little research has examined the impacts of graphic health warnings on the users of smokeless tobacco products. METHODS: A convenience sample of past-month, male smokeless tobacco users (n = 142; 100% male) was randomly assigned to view a smokeless tobacco advertisement with a graphic health warning (GHW) or a text-only warning. Eye-tracking equipment measured viewing time, or dwell time, in milliseconds. Following the advertisement exposure, participants self-reported smokeless tobacco craving and recalled any content in the health warning message (unaided recall). Linear and logistic regression analyses evaluated the proportion of time viewing the GHW, craving, and GHW recall. RESULTS: Participants who viewed a GHW spent a significantly greater proportion of their ad viewing time on GHWs (2.87 seconds or 30%), compared to those viewing a text-only warning (2.05 seconds or 24%). Although there were no significant differences by condition in total advertisement viewing duration, those participants viewing a GHW had increased recall of health warning messages compared to the text-only warning (76% had any warning message recall compared to 53%; p < .05). Self-reported craving after advertisement exposure was lower in the GHW compared to text-only condition, but the difference was not statistically significant (a rating of 4.4 vs. 5.3 on a 10-point scale; p = .08). CONCLUSIONS: GHWs attracted greater attention and greater recall of health warning messages compared to text-only warnings among rural male smokeless tobacco users. IMPLICATIONS: Among a sample of rural smokeless tobacco users, GHWs attracted more attention and recall of health warning messages compared to text-only warnings when viewed within smokeless tobacco advertising. These findings provide additional empirical support that GHWs are an effective tobacco control tool for all tobacco products and advertisements.