Promoting Healthy Adolescent Romantic Relationships: Results of a Multisite, Two-group Parallel Randomized Clinical Trial.

PURPOSE: To examine the impact of About Us, an innovative healthy relationships intervention that promotes positive adolescent romantic relationships and the use of effective contraceptives, on improving behavior, attitudes, and intentions related to sexual intercourse, relationship communication, and conflict resolution at 3- and 9-month follow-up, compared to services as usual. METHODS: This was a multi-site, two-group, parallel, randomized-controlled trial with an intervention/comparison allocation ratio of 3:2 conducted at seven high schools in California between February 2018 and May 2021. RESULTS: Overall, our study did not find statistically significant evidence of improved behavior, attitudes, and intentions related to sexual intercourse, relationship communication, and conflict resolution among participants (14-18 years old) randomized to the intervention group (n = 316) compared to services as usual (n = 217) during follow-up (group x time; p > .05). Exploratory within group analyses showed that, compared to baseline, at the 3-month follow-up, the prevalence of reporting having had sex increased in the control group relative to intervention group (+19% vs. +9%, p < .01). Our sub-group analyses showed that changes in condom use intentions scores differed across school sites (group x time x school; p < .01); mixed (positive and negative) trends were observed for intervention effect, and schools with positive intervention effect trends tended to have greater program participation. DISCUSSION: About Us did not show statistically significant positive impacts on primary or secondary outcomes as anticipated. Our exploratory findings show evidence of some promising trends of intervention effects at the school-level, suggesting a need for better tailored intervention components and/or delivery to address the unique environmental contexts of participants. Overall, the context of study implementation was negatively affected by the COVID-19 pandemic and challenges related to using a non-classroom delivery intervention approach. Combined, these factors may have contributed to the study null findings. Moreover, it is difficult to know (or determine) the intervention's impact under more ideal conditions (i.e., no COVID pandemic).

Prevalence and predictors of female sexual dysfunction among sexually active women in the diabetes prevention program outcomes study.

OBJECTIVE: To determine the burden and identify correlates of female sexual dysfunction (FSD) among women with prediabetes (PreD) and type 2 diabetes (T2D) enrolled in the Diabetes Prevention Program (DPP) Outcomes Study (DPPOS). METHODS: The DPPOS visit included the Female Sexual Function Index (FSFI) to determine sexual function. Of 1464 participants, 1320 (90%) completed the (FSFI) and 426 were sexually active. A backward selection multivariable logistic regression model estimated the odds of FSD for sociodemographic, clinical, and diabetes-related covariates. RESULTS: One hundred and eighty-five (43%) had a score of ≤26.55 and met the criteria for FSD. After adjustment for DPP treatment and age, urinary incontinence (UI) (odds ratio [OR] = 1.91, 95% confidence interval [CI] = 1.15-3.17) and hysterectomy (OR = 1.89, 95% CI = 1.01-3.53) were associated with increased odds of FSD. Increased body mass index was protective for FSD (OR = 0.93 per kg/m2, 95% CI = 0.89-0.96). Michigan Neuropathy Screening Instrument-based peripheral neuropathy (mean±SD scores 1.1±1.3 vs. 0.9±1.1, p < 0.0001) and Electrocardiogram (ECG)-based autonomic dysfunction measures (mean ± SD heart rate levels 64.3 ± 6.8 vs. 65.6 ± 10.2, p = 0.008) were associated with FSD. There were no differences in diabetes rates between women who did (66.5%) and did not (66%) have (p = 0.7). CONCLUSIONS: FSD is prevalent in women with PreD and T2D. Our findings suggest that FSD is associated with neuropathic complications commonly observed in PreD and T2D.

Correlates of early breastfeeding cessation and breastmilk expression in Uganda: a case-control study.

OBJECTIVE: To identify the correlates of early breastfeeding (BF) cessation and breastmilk expression (BE) among mothers 12 months after childbirth. METHODS: We used a case-control study design to compare characteristics between mothers who stopped BF and expressed breastmilk 12 months after childbirth in Uganda. BF practices were determined in 12-month follow-up interviews using an adapted World Health Organization infant feeding questionnaire. Univariate and bivariate logistic regression models identified correlates of early BF cessation and BE as distinct but related outcomes. RESULTS: The odds of early BF cessation were higher among mothers who expressed breastmilk irrespective of maternal age (adjusted odds ratio: 2.82; 95% confidence interval: 1.39, 5.68). Mothers who stopped BF and did not express breastmilk were more likely to be older than those who continued BF and did not express breastmilk during the first 12 postpartum months. CONCLUSION: Mothers living with human immunodeficiency virus infection have disproportionately high odds of early BF cessation that may contribute to disparities in child health outcomes. Promotion of safe BF practices coupled with family and social support could be a viable preventive strategy for attenuating such disparities, especially among young mothers at risk of early BF cessation.

Race/ethnic differences in the association of anxiety, depression, and discrimination with subsequent nicotine and cannabis use among young adults: A prospective longitudinal study.

INTRODUCTION: The shifting patterns in nicotine and cannabis use among young adults is taking place at a time when there is also increased reports of psychosocial stressors such as anxiety, depression, and everyday discrimination. Although race/ethnicity has been found to moderate the impact of psychosocial stressors, there is limited research examining the association of anxiety, depression, and discrimination with patterns of nicotine and/or cannabis product use among diverse young adults. METHODS: Data were from a longitudinal study of 2478 US young adults surveyed between 2019 and 2021. General estimating equation models were used to examine associations of self-reported psychological symptoms (depression, anxiety) and social stressors (discrimination) with substance use (any nicotine and cannabis product use; nicotine and cannabis vaping). RESULTS: Young adults from different racial/ethnic groups differed significantly in their depression and discrimination scores with young adults of color having higher mean scores. Overall, higher depression and everyday discrimination score was associated with increased odds of past 6-month use of any nicotine/tobacco and cannabis products. Higher generalized anxiety score increased odds of any nicotine/tobacco and dual nicotine and cannabis product use. Higher everyday discrimination score was associated with increased odds nicotine and cannabis vaping overall. Stratified models showed variation in associations among different racial/ethnic groups. CONCLUSIONS: Psychosocial stressors are associated with increased substance use odds among young adults. However, these stressors have a differential impact on substance use odds among young adults from different racial/ethnic contexts.

Prevalence and predictors of erectile dysfunction among men in the diabetes prevention program outcomes study.

OBJECTIVE: To determine burden and identify correlates of erectile dysfunction (ED) among men with prediabetes (PreD) and type 2 diabetes (T2D) enrolled in the Diabetes Prevention Program (DPP) Outcomes Study (DPPOS). RESEARCH DESIGN AND METHODS: The 2017 DPPOS visit included administration of the International Index of Erectile Function. Of 648 male participants, 88 % (n = 568) completed the survey. Associations between sociodemographic, behavioral, clinical, and glycemic measures at time of ED assessment, and ED were examined using multivariable logistic regression models in men with PreD and T2D separately. RESULTS: Overall, 218 (38 %) men met ED criteria. Prevalence was similar in men with PreD (41 %) and T2D (37 %) (p = 0.4). In all men, age (p < 0.001) increased odds of ED. Among men with PreD, those assigned to intensive lifestyle intervention (ILS), but not metformin, had decreased odds of ED compared with the placebo group (OR = 0.35, 95 % CI = 0.13, 0.94). Non-Hispanic White race was associated with increased odds of ED compared with other races (OR = 4.3; 95 % CI = 1.92, 9.65). Among men with T2D, ED risk did not differ by DPP treatment assignment; however, individuals with metabolic syndrome defined by National Cholesterol Education Program criteria, had increased odds of ED (OR = 1.85, 95 % CI = 1.14, 3.01), as did individuals with depression (OR = 2.05; 95 % CI = 1.10, 3.79). CONCLUSIONS: ED is prevalent in men with PreD and T2D. Our finding of reduced odds of ED in men randomized to ILS and with PreD suggests a potential opportunity for risk mitigation in the prediabetes interval. In men who have progressed to T2D, metabolic factors appear to be associated with ED.

Body mass index trajectories and mortality risk in Japan using a population-based prospective cohort study: the Japan Public Health Center-based Prospective Study.

BACKGROUND: Recent studies have found that long-term changes in weight during adulthood are associated with a high risk of mortality. The objective of this study was to characterize body mass index (BMI) trajectories during adulthood and to examine the association between BMI trajectories and risk of death in the Japanese population. METHODS: The data were extracted from Japan Public Health Center-based Prospective Study-a population-based prospective cohort study in Japan with participants aged 40-69 years followed over 20 years. The participants were categorized into multiple BMI trajectory groups using the latent class growth model. The Cox proportional-hazards model was conducted using all-cause mortality and cause-specific mortality as outcomes and the identified BMI trajectory groups as a predictor. In total, 65 520 participants were included in the analysis. RESULTS: Six BMI trajectory groups were identified: underweight stable (Group 1), low-to-high normal (Group 2), high-to-low normal (Group 3), normal to overweight (Group 4), overweight to normal (Group 5) and normal to obese (Group 6). Our Cox models showed a higher hazard (risk) of all-cause mortality among participants in the BMI-declining groups [Group 3, adjusted hazard ratio (aHR): 1.10, 95% CI: 1.05-1.16; Group 5, aHR: 1.16, 95% CI: 1.08-1.26], underweight stable group (Group 1, aHR: 1.27, 95% CI: 1.21-1.33) and normal to obese group (Group 6, aHR: 1.22, 95% CI: 1.13-1.33) than Group 2 (low-to-high normal BMI trajectory). CONCLUSIONS: Stable underweight and weight loss were associated with a high risk of mortality, both of which were uniquely observed in a Japanese population.

Asthma innovations from the first International Collaborative Asthma Network forum.

Background: Many patients have uncontrolled asthma despite available treatments. Most of the new asthma therapies have focused on type 2 (T2) inflammation, leaving an unmet need for innovative research into mechanisms of asthma beyond T2 and immunity. An international group of investigators developed the International Collaborative Asthma Network (ICAN) with the goal of sharing innovative research on disease mechanisms, developing new technologies and therapies, organising pilot studies and engaging early-stage career investigators from across the world. This report describes the purpose, development and outcomes of the first ICAN forum. Methods: Abstracts were solicited from interdisciplinary early-stage career investigators with innovative ideas beyond T2 inflammation for asthma and were selected for presentation at the forum. Breakout sessions were conducted to discuss innovation, collaboration and research translation. Results: The abstracts were categorised into: 1) general omics and big data analysis; 2) lung-brain axis and airway neurology; 3) sex differences; 4) paediatric asthma; 5) new therapeutic targets inspired by airway epithelial biology; 6) new therapeutics targeting airway and circulating immune mediators; and 7) lung anatomy, physiology and imaging. Discussions revealed that research groups are looking for opportunities to further their findings using larger scale collaboration and the ability to translate their in vitro findings into clinical treatment. Conclusions: Through ICAN, teams that included interdisciplinary early-stage career investigators discussed innovation, collaboration and translation in asthma and severe asthma research. With a combination of fresh ideas and energetic, collaborative, global participation, ICAN has laid a firm foundation and model for future collaborative global asthma research.

Service Utilization among Persons Who Inject Drugs Attending a Syringe Exchange Program in New York State.

BACKGROUND: Epidemiologic studies commonly recommend the integration of harm reduction programs with health and social services to improve the well-being of persons who inject drugs (PWIDs). This study identified service utilization clusters for PWIDs attending a syringe exchange program (SEP) in 2017 to better understand in-house service usage. METHODS: We applied Multiple Correspondence Analysis and Hierarchical Clustering on Principal Components to classify 475 PWIDs into clusters using anonymized, SEP records data from New York. Multinomial logistic regression was used to identify sociodemographic and program engagement correlates of cluster membership. RESULTS: Only 22% of participants utilized at least one service. We identified three clusters of service utilization defined by 1) Nonuse; 2) Support, Primary Care, & Maintenance service use; and 3) HIV/STD, Support, Primary Care, & Maintenance service use. Cluster 2 members were less likely to be living alone compared to Cluster 1 (AOR = 0.08, 95% CI: 0.04, 0.17) while Cluster 3 members were less likely to be White (AOR = 0.19, 95% CI: 0.07, 0.50) or living alone (AOR = 0.16, 95% CI: 0.06, 0.44) and more likely to be Medicaid recipients (AOR = 2.89, 95% CI: 1.01, 8.36) compared to Cluster 1. Greater than one SEP interaction, lower syringe return ratios, and being a long-term client increased the odds of service utilization. DISCUSSION: Overall, PWID clients had a low prevalence of in-house service use particularly those who live alone. However, higher service utilization was observed among more vulnerable populations (i.e., non-White and LGBT). Future research is needed to profile services used outside of the SEP.

Risk and Protective Factors Associated with Adverse Childhood Experiences in Vulnerable Families: Results of a Randomized Clinical Trial of SafeCare®.

Early adversity predicts increased risk for mental and physical health problems. As such, intervention efforts, such as home-based parenting programs, have been initiated with vulnerable families to reduce adversity exposure and promote child well-being. The present randomized clinical trial had a parallel design and 1:1 allocation ratio of SafeCare augmented for an urban high-risk population (SC+) compared to standard home-based mental health services (SAU) to examine risk and protective factors proximal to child maltreatment. Parents (N=562) of young children (5 years or less) at risk of depression, intimate partner violence, or substance abuse were randomized to SC+ or SAU. A significant program effect was found in favor of SC+ for parental depression and social support, as well as within-group improvements for both groups in depression, intimate partner victimization, family resources, and social support. Promising next steps include future trials examining how improvements in parental depression and social support impact child well-being over time and further augmentation of SafeCare to enhance healthy relationships and address cultural congruency of services.

Risk of Type 2 Diabetes Among Individuals with Excess Weight: Weight Trajectory Effects.

PURPOSE OF REVIEW: Increased risk of type 2 diabetes mellitus (T2D) among individuals with overweight or obesity is well-established; however, questions remain about the temporal dynamics of weight change (gain or loss) on the natural course of T2D in this at-risk population. Existing epidemiologic evidence is limited to studies that discretely sample and assess excess weight and T2D risk at different ages with limited follow-up, yet changes in weight may have time-varying and possibly non-linear effects on T2D risk. Predicting the impact of weight change on the risk of T2D is key to informing primary prevention. We critically review the relationship between weight change, trajectory groups (i.e., distinct weight change patterns), and T2D risk among individuals with excess weight in recently published T2D prevention randomized controlled trials (RCTs) and longitudinal cohort studies. RECENT FINDINGS: Overall, weight trajectory groups have been shown to differ by age of onset, sex, and patterns of insulin resistance or beta-cell function biomarkers. Lifestyle (diet and physical activity), pharmacological, and surgical interventions can modify an individual's weight trajectory. Adolescence is a critical etiologically relevant window during which onset of excess weight may be associated with higher risk of T2D. Changes in insulin resistance and beta-cell function biomarkers are distinct but related correlates of weight trajectory groups that evolve contemporaneously over time. These multi-trajectory markers are differentially associated with T2D risk. T2D risk may differ by the age of onset and duration of excess body weight, and the type of weight loss intervention. A better understanding of the changes in weight, insulin sensitivity, and beta-cell function as distinct but related correlates of T2D risk that evolve contemporaneously over time has important implications for designing and targeting primary prevention efforts.

Maternal major depression disorder misclassification errors: Remedies for valid individual- and population-level inference.

Individual and population level inference about risk and burden of MDD, particularly maternal MDD, is often made using case-finding tools that are imperfect and prone to misclassification error (i.e. false positives and negatives). These errors or biases are rarely accounted for and lead to inappropriate clinical decisions, inefficient allocation of scarce resources, and poor planning of maternal MDD prevention and treatment interventions. The argument that the use of existing maternal MDD case-finding instruments results in misclassification errors is not new; in fact, it has been argued for decades, but by and large its implications and particularly how to correct for these errors for valid inference is unexplored. Correction of the estimates of maternal MDD prevalence, case-finding tool sensitivity and specificity is possible and should be done to inform valid individual and population-level inferences.

Evaluation of the type I error rate when using parametric bootstrap analysis of a cluster randomized controlled trial with binary outcomes and a small number of clusters.

BACKGROUND: Cluster randomized controlled trials (cRCTs) are increasingly used but must be analyzed carefully. We conducted a simulation study to evaluate the validity of a parametric bootstrap (PB) approach with respect to the empirical type I error rate for a cRCT with binary outcomes and a small number of clusters. METHODS: We simulated a case study with a binary (0/1) outcome, four clusters, and 100 subjects per cluster. To compare the validity of the test with respect to error rate, we simulated the same experiment with K=10, 20, and 30 clusters, each with 2,000 simulated datasets. To test the null hypothesis, we used a generalized linear mixed model including a random intercept for clusters and obtained p-values based on likelihood ratio tests (LRTs) using the parametric bootstrap method as implemented in the R package "pbkrtest". RESULTS: The PB test produced error rates of 9.1%, 5.5%, 4.9%, and 5.0% on average across all ICC values for K=4, K=10, K=20, and K=30, respectively. The error rates were higher, ranging from 9.1% to 36.5% for K=4, in the models with singular fits (i.e., ignoring clustering) because the ICC was estimated to be zero. CONCLUSION: Using the parametric bootstrap for cRCTs with a small number of clusters results in inflated error rates and is not valid.

Randomization, design and analysis for interdependency in aging research: no person or mouse is an island.

Investigators traditionally use randomized designs and corresponding analysis procedures to make causal inferences about the effects of interventions, assuming independence between an individual's outcome and treatment assignment and the outcomes of other individuals in the study. Often, such independence may not hold. We provide examples of interdependency in model organism studies and human trials and group effects in aging research and then discuss methodologic issues and solutions. We group methodologic issues as they pertain to (1) single-stage individually randomized trials; (2) cluster-randomized controlled trials; (3) pseudo-cluster-randomized trials; (4) individually randomized group treatment; and (5) two-stage randomized designs. Although we present possible strategies for design and analysis to improve the rigor, accuracy and reproducibility of the science, we also acknowledge real-world constraints. Consequences of nonadherence, differential attrition or missing data, unintended exposure to multiple treatments and other practical realities can be reduced with careful planning, proper study designs and best practices.

Decision tree-based rules outperform risk scores for childhood asthma prognosis.

BACKGROUND: There are no widely accepted prognostic tools for childhood asthma; this is in part due to the multifactorial and time-dependent nature of mechanisms and risk factors that contribute to asthma development. Our study objective was to develop and evaluate the prognostic performance of conditional inference decision tree-based rules using the Pediatric Asthma Risk Score (PARS) predictors as an alternative to the existing logistic regression-based risk score for childhood asthma prediction at 7 years in a high-risk population. METHODS: The Canadian Asthma Primary Prevention Study data were used to develop, compare, and contrast the prognostic performance (area under the curve [AUC], sensitivity, and specificity) of conditional inference tree-based decision rules to the pediatric asthma risk score for the prediction of childhood asthma at 7 years. RESULTS: Conditional inference decision tree-based rules have higher prognostic performance (AUC: 0.85; 95% CI: 0.81, 0.88; sensitivity = 47%; specificity = 93%) than the pediatric asthma risk score at an optimal cutoff of ≥6 (AUC: 0.71; 95% CI: 0.67, 0.76; sensitivity = 60%; specificity = 74%). Moreover, the pediatric asthma risk score is not linearly related to asthma risk, and at any given pediatric asthma risk score value, different combinations of its pediatric asthma risk score clinical variables differentially predict asthma risk. CONCLUSION: Conditional inference tree-based decision rules could be a useful childhood asthma prognostic tool, providing an alternative way to identify unique subgroups of at-risk children, and insights into associations and effect mechanisms that are suggestive of appropriate tailored preventive interventions. However, the feasibility and effectiveness of such decision rules in clinical practice is warranted.

Correlates of disparities in syringe return ratios: A cross-sectional study of a syringe services program in New York.

BACKGROUND: Predictors of syringe exchange behavior are critical to informing secondary prevention measures needed to attenuate risk of blood-borne infections among persons who inject drugs (PWID). METHODS: Participants included PWIDs who attended a syringe services program in New York from 2015 to 2017 (n = 1777). We analyzed the syringe return ratio (receipts/returns) with two distinct but related methodological strategies-threshold logistic regression and quantile regression-to identify correlates of disparities in syringe return ratios. RESULTS: The majority of participants were white males negative for HIV (90% white, 63% male, 76% HIV-). Logistic and quantile regression models showed that the correlates of disparate syringe return ratios (i.e., magnitude and directionality of differences) changed across different percentile groups and quantile levels, respectively. At the median threshold, being single, urbanicity, and older age were associated with higher return ratios. Syringe return ratio disparities were more pronounced among subgroups of nontypical PWIDs (with extremely low or high return ratios) especially by urbanicity, race, relationship status, and type of housing. CONCLUSIONS: Irrespective of urbanicity classification, correlates of syringe return ratios such as older age, Black race, single relationship status, and unstable housing appear to be critical to informing targeted secondary prevention initiatives that promote harm reduction behavior.