Multilevel Interventions and Dental Attendance in Pediatric Primary Care: A Cluster Randomized Clinical Trial.

Importance: Untreated tooth decay is disproportionately present among low-income young children. While American Academy of Pediatrics (AAP) guidelines require pediatric clinicians to implement oral health care, the effectiveness of these oral health interventions has been inconclusive. Objective: To test the effectiveness of multilevel interventions in increasing dental attendance and reducing untreated decay among young children attending well-child visits (WCVs). Design, Setting, and Participants: The Pediatric Providers Against Cavities in Children's Teeth study is a cluster randomized clinical trial that was conducted at 18 pediatric primary care practices in northeast Ohio. The trial data were collected between November 2017 and July 2022, with data analyses conducted from August 2022 to March 2023. Eligible participants included Medicaid-enrolled preschoolers aged 3 to 6 years attending WCVs at participating practices who were enrolled at baseline (WCV 1) and followed-up for 2 consecutive examinations (WCV 2 and WCV 3). Interventions: Clinicians in the intervention group received both the practice-level (electronic medical record changes to document oral health) and clinician-level (common-sense model of self-regulation theory-based oral health education and skills training) interventions. Control group clinicians received AAP-based standard oral health education alone. Main Outcomes and Measures: Dental attendance was determined through clinical dental examinations conducted by hygienists utilizing International Caries Detection and Assessment System criteria and also from Medicaid claims data. Untreated decay was determined through clinical examinations. A generalized estimating equations (GEE) approach was used for both clinical examinations and Medicaid claims data. Results: Eighteen practices were randomized to either intervention or control. Participants included 63 clinicians (mean [SD] age, 47.0 [11.3] years; 48 female [76.2%] and 15 male [23.8%]; 28 in the intervention group [44.4%]; 35 in the control group [55.6%]) and 1023 parent-child dyads (mean [SD] child age, 56.1 [14.0] months; 555 male children [54.4%] and 466 female children [45.6%]; 517 in the intervention group [50.5%]; 506 in the control group [49.5%]). Dental attendance from clinical examinations was significantly higher in the intervention group (170 children [52.0%]) vs control group (150 children [43.1%]) with a difference of 8.9% (95% CI, 1.4% to 16.4%; P = .02). The GEE model using clinical examinations showed a significant increase in dental attendance in the intervention group vs control group (adjusted odds ratio, 1.34; 95% CI, 1.07 to 1.69). From Medicaid claims, the control group had significantly higher dental attendance than the intervention group at 2 years (332 children [79.6%] vs 330 children [73.7%]; P = .04) but not at 3 years. A clinically but not statistically significant reduction in mean number of untreated decay was found in the intervention group compared with controls (B = -0.27; 95% CI, -0.56 to 0.02). Conclusions and Relevance: In this cluster randomized clinical trial, children in the intervention group had better dental outcomes as was evidenced by increased dental attendance and lower untreated decay. These findings suggest that intervention group clinicians comprehensively integrated oral health services into WCVs. Trial Registration: ClinicalTrials.gov Identifier: NCT03385629.

Loneliness and Crowded Living Predicted Poor Health in a Sample of Cancer Patients During COVID-19 Pandemic.

We investigated the influence of social determinants of health (SDOH), healthcare services, and health behaviors on mental and physical health outcomes of cancer patients between the first winter and the following post-vaccine summer of the COVID-19 pandemic. A three-wave online survey of individuals diagnosed with incident cancer between January 2019 and January 2020 was conducted between November of 2020 and August of 2021 in northeast Ohio. Descriptive analysis and mixed-effect regression analyses were performed. A total of 322 newly diagnosed cancer patients, with 40 African Americans and 282 Whites (215 from metropolitan areas and 67 nonmetropolitan) responded to the survey questions. In Wave 3 ending in August 2021, the survey respondents reported significantly reduced depression (p = .019) on the Hamilton Depression Rating Scale and improved global health (p = .036) on PROMIS. With age, comorbidity, and other demographic and medical variables controlled in the analyses, the feeling of loneliness (p < .001) and crowded living space (p = .001, p = .015) were the two most prominent factors associated with depression, irritability, and poor global health at baseline, with the lowest p values and persistent effect. Self-efficacy of taking preventive measures was associated with reduced depression (p = .001) and improved global health (p = .029). Increasing access to medicine (p < .01) and satisfaction with telehealth appointments (p < .01) were significantly associated with better global health and reduced irritability. Respondents who had private health insurance reported better health than those that had Medicare coverage only (p < .05). This longitudinal, observational study demonstrated the impact of SDOH on health outcomes of cancer patients. Substandard living conditions resulting in loneliness and crowdedness, quality of medical care (e.g., quality telehealth and access to medicine), and personal behaviors (e.g., self-efficacy) were significantly associated with health outcomes in newly diagnosed cancer patients during the pandemic and should be given adequate consideration for the purpose of improving clinical care.

Infant Behaviors, Prenatal Cocaine Exposure, and Adult Intelligence.

Importance: Linking prenatal drug exposures to both infant behavior and adult cognitive outcomes may improve early interventions. Objective: To assess whether neonatal physical, neurobehavioral, and infant cognitive measures mediate the association between prenatal cocaine exposure (PCE) and adult perceptual reasoning IQ. Design, Setting, and Participants: This study used data from a longitudinal, prospective birth cohort study with follow-up from 1994 to 2018 until offspring were 21 years post partum. A total of 384 (196 PCE and 188 not exposed to cocaine [NCE]) infants and mothers were screened for cocaine or polydrug use. Structural equation modeling was performed from June to November 2023. Exposures: Prenatal exposures to cocaine, alcohol, marijuana, and tobacco assessed through urine and meconium analyses and maternal self-report. Main Outcomes and Measures: Head circumference, neurobehavioral assessment, Bayley Scales of Infant Development, Fagan Test of Infant Intelligence score, Wechsler Perceptual Reasoning IQ, Home Observation for Measurement of the Environment (HOME) score, and blood lead level. Results: Among the 384 mothers in the study, the mean (SD) age at delivery was 27.7 (5.3) years (range, 18-41 years), 375 of 383 received public assistance (97.9%) and 336 were unmarried (87.5%). Birth head circumference (standardized estimate for specific path association, -0.05, SE = 0.02; P = .02) and 1-year Bayley Mental Development Index (MDI) (standardized estimate for total of the specific path association, -0.05, SE = 0.02; P = .03) mediated the association of PCE with Wechsler Perceptual Reasoning IQ, controlling for HOME score and other substance exposures. Abnormal results on the neurobehavioral assessment were associated with birth head circumference (ß = -0.20, SE = 0.08; P = .01). Bayley Psychomotor Index (ß = 0.39, SE = 0.05; P < .001) and Fagan Test of Infant Intelligence score (ß = 0.16, SE = 0.06; P = .01) at 6.5 months correlated with MDI at 12 months. Conclusions and Relevance: In this cohort study, a negative association of PCE with adult perceptual reasoning IQ was mediated by early physical and behavioral differences, after controlling for other drug and environmental factors. Development of infant behavioral assessments to identify sequelae of prenatal teratogens early in life may improve long-term outcomes and public health awareness.

Association of School Instructional Mode with Community COVID-19 Incidence during August-December 2020 in Cuyahoga County, Ohio.

Remote and hybrid modes of instruction were employed as alternatives to in-person instruction as part of early mitigation efforts in response to the COVID-19 pandemic. We investigated the impact of a public school district's instructional mode on cumulative incidence and transmission in the surrounding community by employing a generalized estimating equations approach to estimate the association with weekly COVID-19 case counts by zip code in Cuyahoga County, Ohio, from August to December 2020. Remote instruction only (RI) was employed by 7 of 20 school districts; 13 used some non-remote instruction (NRI) (2-15 weeks). Weekly incidence increased in all zip codes from August to peak in late fall before declining. The zip code cumulative incidence within NRI school districts was higher than in those offering only RI (risk ratio = 1.12, p = 0.01; risk difference = 519 per 100,000, 95% confidence interval (123-519)). The mean effect for NRI on emergent cases 2 weeks after mode exposure, controlling for Social Vulnerability Index (SVI), was significant only for high SVI zip codes 1.30, p < 0.001. NRI may be associated with increased community COVID-19 incidence, particularly in communities with high SVI. Vulnerable communities may need more resources to open schools safely.

Barriers to dental utilization among Medicaid-enrolled young children from primary care practices in Northeast Ohio.

OBJECTIVES: To evaluate the individual and community factors that contribute to dental utilization among young children on Medicaid utilizing the Anderson Model and the Socio-Ecological Framework. METHODS: This observational cross-sectional study was conducted using baseline data (socio-demographics, clinical dental need) from a cluster-randomized hybrid effectiveness-implementation trial among 1021 child-parent dyads recruited from primary care practices across northeast Ohio. The baseline data were then linked to dental Medicaid claims data (categorized as any dental visit, volume, and type in the past 12 months) and ICD-10 codes from the child's EHR data (individual-level) together with Dental Health Provider Shortage Area (HPSA) status and Area Deprivation Index (ADI) which were obtained at the neighbourhood-level using home address of each dyad (community-level). Multivariable analyses using generalized estimating equations (GEE) accounted for clustering by practice, and models included individual-level alone, and individual + community-level factors to evaluate their effects on dental utilization. RESULTS: Medicaid claims data indicated that among the 1021 children (mean age: 4.3 ± 1.1 years; 54.4% males; 43.8% Black, Non-Hispanic), a majority of children were seeing the dentist at least once a year by the age of 4 (56.1%). The mean ADI of their neighbourhoods was 109.22 (20.2) and 27.5% lived in a HPSA area. The GEE analyses revealed that individual factors such as older children, parents being married, and continuous Medicaid enrollment were associated with significantly higher dental utilization. Among community factors, being in a HPSA had an OR = 1.53 (CI: 1.03, 2.27) associated with higher dental utilization. CONCLUSIONS: Being in a HPSA was associated with higher dental utilization possibly due to dentists or safety net dental clinics in these areas accepting Medicaid-eligible children.

Treatment Patterns and Survival Outcomes in Patients With Breast Cancer on Medicaid, Pre- and Post-Expansion.

BACKGROUND: The objective of this study was to evaluate the impact of Medicaid expansion on breast cancer treatment and survival among Medicaid-insured women in Ohio, accounting for the timing of enrollment in Medicaid relative to their cancer diagnosis and post-expansion heterogeneous Medicaid eligibility criteria, thus addressing important limitations in previous studies. METHODS: Using 2011-2017 Ohio Cancer Incidence Surveillance System data linked with Medicaid claims data, we identified women aged 18 to 64 years diagnosed with local-stage or regional-stage breast cancer (n=876 and n=1,957 pre-expansion and post-expansion, respectively). We accounted for women's timing of enrollment in Medicaid relative to their cancer diagnosis, and flagged women post-expansion as Affordable Care Act (ACA) versus non-ACA, based on their income eligibility threshold. Study outcomes included standard treatment based on cancer stage and receipt of lumpectomy, mastectomy, chemotherapy, radiation, hormonal treatment, and/or treatment for HER2-positive tumors; time to treatment initiation (TTI); and overall survival. We conducted multivariable robust Poisson and Cox proportional hazards regression analysis to evaluate the independent associations between Medicaid expansion and our outcomes of interest, adjusting for patient-level and area-level characteristics. RESULTS: Receipt of standard treatment increased from 52.6% pre-expansion to 61.0% post-expansion (63.0% and 59.9% post-expansion in the ACA and non-ACA groups, respectively). Adjusting for potential confounders, including timing of enrollment in Medicaid, being diagnosed in the post-expansion period was associated with a higher probability of receiving standard treatment (adjusted risk ratio, 1.14 [95% CI, 1.06-1.22]) and shorter TTI (adjusted hazard ratio, 1.14 [95% CI, 1.04-1.24]), but not with survival benefits (adjusted hazard ratio, 1.00 [0.80-1.26]). CONCLUSIONS: Medicaid expansion in Ohio was associated with improvements in receipt of standard treatment of breast cancer and shorter TTI but not with improved survival outcomes. Future studies should elucidate the mechanisms at play.

Prenatal cocaine exposure and self-reported behavioral adjustments from ages 12 to 21: environmental pathways.

BACKGROUND: In a birth-cohort study, we followed offspring with prenatal cocaine exposure (PCE) to investigate longitudinal associations of PCE with self-reported behavioral adjustment from early adolescence to emerging adulthood (EA). Environmental pathways (family functioning, non-kinship care, maltreatment) were specified as potential mediators of PCE. METHODS: Participants were 372 (190 PCE; 47% male), primarily Black, low socioeconomic status, enrolled at birth. Internalizing and externalizing behaviors were assessed using Youth Self-Report at ages 12 and 15 and Adult Self-Report at age 21. Extended random-intercept cross-lagged panel modeling was used to account for potential bidirectional relationships between internalizing and externalizing behaviors over time, examining potential mediators. RESULTS: Adjusting for covariates, significant indirect effects were found for each mediator at different ages. For family functioning, these were both internalizing (ß = 0.83, p = 0.04) and externalizing behaviors (ß = 1.58, p = 0.02) at age 12 and externalizing behaviors at age 15 (ß = 0.51, p = 0.03); for non-kinship care, externalizing behaviors at ages 12 (ß = 0.63, p = 0.02) and 15 (ß = 0.20, p = 0.03); and for maltreatment, both internalizing and externalizing behaviors at ages 15 (ß = 0.64, p = 0.02 for internalizing; ß = 0.50, p = 0.03 for externalizing) and 21 (ß = 1.39, p = 0.01 for internalizing; ß = 1.11, p = 0.01 for externalizing). Direct associations of PCE with internalizing and externalizing behaviors were not observed, nor cross-lagged relationships between internalizing and externalizing behaviors. CONCLUSIONS: Negative associations of PCE with behavioral adjustment persist into EA via environmental pathways, specifying intervention points to disrupt adverse pathways toward healthy development.

Characterizing causal relationships of visceral fat and body shape on multiple sclerosis risk.

BACKGROUND: Epidemiologic studies have established obesity as a risk factor for multiple sclerosis (MS). These studies relied on body-mass index (BMI) and body size silhouettes as the primary measures of obesity. Unfortunately, the causal mechanisms through which obesity confers MS risk are not yet known. OBJECTIVES: To investigate the causal effects of multiple specific measures of body fat on MS risk in populations of European descent, using Mendelian randomization (MR). METHODS: MR is a genetic instrumental variable analysis utilizing genome-wide association (GWA) summary statistics to infer causality between phenotypes. MR analyses were performed to investigate the relationships between seven measures of body fat (BMI, waist-hip ratio, visceral adipose tissue [VAT], subcutaneous adipose tissue, and arm-, leg-, and trunk-fat to total body fat ratio) and MS risk. RESULTS: Only BMI and VAT were significantly associated with MS risk in separate MR analyses (ßBMI=0.27, pBMI<0.001; ßVAT=0.28, pVAT=0.006). High correlation between BMI and VAT instruments suggest that two-sample MR associations for BMI and VAT likely capture the same causal mechanisms. CONCLUSIONS: BMI and VAT were causally associated with MS risk in European populations, though their effects do not appear independent, suggesting overlap in the role of overall body mass and visceral obesity in MS pathogenesis.

Accounting for Medicaid expansion and regional policy and programs to advance equity in cancer prevention in the United States.

BACKGROUND: Many studies compare state-level outcomes to estimate changes attributable to Medicaid expansion. However, it is imperative to conduct more granular, demographic-level analyses to inform current efforts on cancer prevention among low-income adults. Therefore, the authors compared the volume of patients with cancer and disease stage at diagnosis in Ohio, which expanded its Medicaid coverage in 2014, with those in Georgia, a nonexpansion state, by cancer site and health insurance status. METHODS: The authors used state cancer registries from 2010 to 2017 to identify adults younger than 64 years who had incident female breast cancer, cervical cancer, or colorectal cancer. Multivariable Poisson regression was conducted by cancer type, health insurance, and state to examine the risk of late-stage disease, adjusting for individual-level and area-level covariates. A difference-in-differences framework was then used to estimate the differences in risks of late-stage diagnosis in Ohio versus Georgia. RESULTS: In Ohio, the largest increase in all three cancer types was observed in the Medicaid group after Medicaid expansion. In addition, significantly reduced risks of late-stage disease were observed among patients with breast cancer on Medicaid in Ohio by approximately 7% and among patients with colorectal cancer on Medicaid in Ohio and Georgia after expansion by approximately 6%. Notably, the authors observed significantly reduced risks of late-stage diagnosis among all patients with colorectal cancer in Georgia after expansion. CONCLUSIONS: More early stage cancers in the Medicaid-insured and/or uninsured groups after expansion suggest that the reduced cancer burden in these vulnerable population subgroups may be attributed to Medicaid expansion. Heterogeneous risks of late-stage disease by cancer type highlight the need for comprehensive evaluation frameworks, including local cancer prevention efforts and federal health policy reforms. PLAIN LANGUAGE SUMMARY: This study looked at how Medicaid expansion affected cancer diagnosis and treatment in two states, Ohio and Georgia. The researchers found that, after Ohio expanded their Medicaid program, there were more patients with cancer among low-income adults on Medicaid. The study also found that, among people on Medicaid, there were lower rates of advanced cancer at the time of diagnosis for breast cancer and colon cancer in Ohio and for colon cancer in Georgia. These findings suggest that Medicaid expansion may be effective in reducing the cancer burden among low-income adults.

Cognitive, social, and health functioning of children with TBI engaged in a formal support program.

BACKGROUND: Students with traumatic brain injury (TBI) often demonstrate difficulties that impact their successful return to school (RTS). OBJECTIVE: To explore injury severity, age at injury, and time since injury as predictors for performance on measures of cognitive, social and health functioning for students' participating in a formal RTS cohort at the time of their enrollment in the School Transition After Traumatic Brain Injury (STATBI) research project. METHODS: Outcome measures across cognitive, social, and health domains were analyzed for association with the explanatory variables of interest using quantile regressions and ordinary least squares regression, as appropriate. RESULTS: Students (N = 91) injured after age 13 showed significantly lower cognitive outcomes than students whose injury occurred earlier. Additionally, students more than one-year post-injury demonstrated poorer social outcome on one measure compared to students whose injury occurred more recently. Health outcomes showed no significant association to any predictors. CONCLUSION: The results of this analysis provide a baseline for a group of students with TBI as they enter a RTS research study. This data can now be paired with longitudinal measures and qualitative data collected simultaneously to gain a deeper understanding of how students with TBI present for RTS.

Dental Caries in Medicaid-Insured Preschool Children With or Without Special Health Care Needs in Northeast Ohio.

Importance: Children with special health care needs (CSHCN) are recognized to be at increased risk of developing dental caries (decay). Evidence is mixed regarding the association of preventive oral health care delivered by pediatric primary care clinicians with caries experience among CSHCN. Objective: To investigate caries experience, including untreated decay, among Medicaid-enrolled preschoolers with or without special health care needs. Design, Setting, and Participants: This cross-sectional study used baseline data from the Pediatric Providers Against Cavities in Children's Teeth study, a cluster-randomized hybrid effectiveness-implementation trial conducted among 1022 Medicaid-enrolled preschoolers aged 3 to 6 years attending well-child visits at 18 participating community pediatric primary care practices in northeast Ohio. Baseline data were collected from November 1, 2017, to August 31, 2019, with statistical analyses conducted from April to August 2022. Exposures: Presence of special health care needs, as assessed by applying the Pediatric Medical Complexity Algorithm to International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes, was abstracted from electronic medical records. CSHCN were defined as having either noncomplex chronic disease (presence of only 1 nonprogressive chronic condition, or multiple nonprogressive chronic conditions in a single body system) or complex chronic disease (presence of any progressive chronic condition, malignant neoplasm, or significant chronic conditions involving multiple body systems). Main Outcomes and Measures: Untreated dental decay and caries experience as assessed through clinical dental examinations using International Caries Detection and Assessment System criteria. Results: A total of 1022 children aged 3 to 6 years from 18 practices were enrolled in the study. The mean (SD) age of the study population was 4.3 (1.1) years, 554 (54.2%) were boys, and of 988 with data on race and ethnicity, 451 (45.6%) were Black. Of these, 301 of 1019 (29.5%) had a likely special health care need (225 with noncomplex chronic conditions and 76 with complex chronic conditions). The most frequent chronic conditions included asthma (n = 209) and mental or behavioral health disorders (n = 146), including attention-deficit/hyperactivity disorder, autism, and developmental delays. Overall, 296 children (29.0%) had untreated decay, and 378 (37.0%) had caries experience (decayed and filled teeth). Accounting for sociodemographic characteristics, CSHCN had 34% reduced odds of untreated decay (adjusted odds ratio [AOR], 0.66 [95% CI, 0.48-0.92]) compared with those with without chronic disease. In addition, caries experience was lower among CSHCN (AOR, 0.79 [95% CI, 0.60-1.04]). Conclusions and Relevance: In this cross-sectional study of Medicaid-enrolled children who attended well-child visits as preschoolers, untreated dental decay was lower among CSHCN compared with those without chronic conditions. This study suggests that CSHCN may have had better access to the various types of dental care facilitated in medical settings.

Increased Hazard Risk of First Malignancy in Adults with Undetectable Serum IgE: a Retrospective Cohort Study.

PURPOSE: The clinical relevance of IgE-deficiency is not established. Previous studies have postulated a relationship between absent serum IgE and the incidence of specific malignancies. We sought to examine the relationship between undetectable total serum IgE (< 3 IU/mL) and first malignancy, considering both general all-cause malignancy risk and risk of specific malignancy subtypes in adult subjects. METHODS: Retrospective cohort study at a single center of 39,965 adults aged 18 or older (median age 51, 65.1% female) with at least one serum total IgE measurement from 1998 to 2020. Analytics included chi2 table and logistic regression modeling of the main outcome measures, which include diagnosis of first malignancy and first diagnosis of specific malignancy subtype. RESULTS: Of the entire cohort, 2584 subjects (6.5%) developed a first malignancy and 2516 (6.3%) had an undetectable IgE. Of those with undetectable IgE levels, 8.9% developed a first malignancy versus 6.3% with detectable IgE measurements. After adjusting for risk factors, there was a significant association between undetectable IgE and risk/hazard of first malignancy (relative risk 1.49, 95% confidence interval (CI) 1.27-1.75) (hazard ratio 1.28, 95% CI 1.08-1.52). Results were similar in multiple sensitivity analyses. For type of malignancy developed, undetectable IgE was associated with increased risk of hematologic malignancy (relative risk 2.07, 95% CI 1.29-3.30) and skin malignancy (relative risk 1.52, 95% CI 1.13-2.05). CONCLUSION: Compared to individuals with detectable IgE levels, patients with undetectable total serum IgE had increased risk and hazard of first malignancy in general, and increased risk of hematologic malignancy in particular.

Community Members as Reviewers of Medical Journal Manuscripts: a Randomized Controlled Trial.

BACKGROUND: Community members may provide useful perspectives on manuscripts submitted to medical journals. OBJECTIVE: To determine the impact of community members reviewing medical journal manuscripts. DESIGN: Randomized controlled trial involving 578 original research manuscripts submitted to two medical journals from June 2018 to November 2021. PARTICIPANTS: Twenty-eight community members who were trained, supervised, and compensated. INTERVENTIONS: A total of 289 randomly selected control manuscripts were reviewed by scientific reviewers only. And 289 randomly selected intervention manuscripts were reviewed by scientific reviewers and one community member. Journal editorial teams used all reviews to make decisions about acceptance, revision, or rejection of manuscripts. MAIN MEASURES: Usefulness of reviews to editors, content of community reviews, and changes made to published articles in response to community reviewer comments. KEY RESULTS: Editor ratings of community and scientific reviews averaged 3.1 and 3.3, respectively (difference 0.2, 95% confidence interval [CI] 0.1 to 0.3), on a 5-point scale where a higher score indicates a more useful review. Qualitative analysis of the content of community reviews identified two taxonomies of themes: study attributes and viewpoints. Study attributes are the sections, topics, and components of manuscripts commented on by reviewers. Viewpoints are reviewer perceptions and perspectives on the research described in manuscripts and consisted of four major themes: (1) diversity of study participants, (2) relevance to patients and communities, (3) cultural considerations and social context, and (4) implementation of research by patients and communities. A total of 186 community reviewer comments were integrated into 64 published intervention group articles. Viewpoint themes were present more often in 66 published intervention articles compared to 54 published control articles (2.8 vs. 1.7 themes/article, difference 1.1, 95% CI 0.4 to 1.8). CONCLUSIONS: With training, supervision, and compensation, community members are able to review manuscripts submitted to medical journals. Their comments are useful to editors, address topics relevant to patients and communities, and are reflected in published articles. TRIAL REGISTRATION: ClinicalTrials.gov NCT03432143.

Post-Affordable Care Act Improvements in Cancer Stage Among Ohio Medicaid Beneficiaries Resulted From an Increase in Stable Coverage.

BACKGROUND: The mechanisms underlying improvements in early-stage cancer at diagnosis following Medicaid expansion remain unknown. We hypothesized that Medicaid expansion allowed for low-income adults to enroll in Medicaid before cancer diagnosis, thus increasing the number of stably-enrolled relative to those who enroll in Medicaid only after diagnosis (emergently-enrolled). METHODS: Using data from the 2011-2017 Ohio Cancer Incidence Surveillance System and Medicaid enrollment files, we identified individuals diagnosed with incident invasive breast (n=4850), cervical (n=1023), and colorectal (n=3363) cancer. We conducted causal mediation analysis to estimate the direct effect of pre- (vs. post-) expansion on being diagnosed with early-stage (-vs. regional-stage and distant-stage) disease, and indirect (mediation) effect through being in the stably- (vs. emergently-) enrolled group, controlling for individual-level and area-level characteristics. RESULTS: The percentage of stably-enrolled patients increased from 63.3% to 73.9% post-expansion, while that of the emergently-enrolled decreased from 36.7% to 26.1%. The percentage of patients with early-stage diagnosis remained 1.3-2.9 times higher among the stably-than the emergently-enrolled group, both pre-expansion and post-expansion. Results from the causal mediation analysis showed that there was an indirect effect of Medicaid expansion through being in the stably- (vs. emergently-) enrolled group [risk ratios with 95% confidence interval: 1.018 (1.010-1.027) for breast cancer, 1.115 (1.064-1.167) for cervical cancer, and 1.090 (1.062-1.118) for colorectal cancer. CONCLUSION: We provide the first evidence that post-expansion improvements in cancer stage were caused by an increased reliance on Medicaid as a source of stable insurance coverage.

A randomized controlled trial of customized adherence enhancement (CAE-E): study protocol for a hybrid effectiveness-implementation project.

BACKGROUND: Mood-stabilizing medications are a cornerstone of treatment for people with bipolar disorder, though approximately half of these individuals are poorly adherent with their medication, leading to negative and even severe health consequences. While a variety of approaches can lead to some improvement in medication adherence, there is no single approach that has superior adherence enhancement and limited data on how these approaches can be implemented in clinical settings. Existing data have shown an increasing need for virtual delivery of care and interactive telemedicine interventions may be effective in improving adherence to long-term medication. METHODS: Customized adherence enhancement (CAE) is a brief, practical bipolar-specific approach that identifies and targets individual patient adherence barriers for intervention using a flexibly administered modular format that can be delivered via telehealth communications. CAE is comprised of up to four standard treatment modules including Psychoeducation, Communication with Providers, Medication Routines, and Modified Motivational Interviewing. Participants will attend assigned module sessions with an interventionist based on their reasons for non-adherence and will be assessed for adherence, functioning, bipolar symptoms, and health resource use across a 12-month period. Qualitative and quantitative data will also be collected to assess barriers and facilitators to CAE implementation and reach and adoption of CAE among clinicians in the community. DISCUSSION: The proposed study addresses the need for practical adherence interventions that are effective, flexible, and designed to adapt to different settings and patients. By focusing on a high-risk, vulnerable group of people with bipolar disorder, and refining an evidence-based approach that will integrate into workflow of public-sector care and community mental health clinics, there is substantial potential for improving bipolar medication adherence and overall health outcomes on a broad level. TRIAL REGISTRATION: The study was registered on ClinicalTrials.gov NCT04622150 on November 9, 2020.

Mass drug administration of ivermectin, diethylcarbamazine, plus albendazole compared with diethylcarbamazine plus albendazole for reduction of lymphatic filariasis endemicity in Papua New Guinea: a cluster-randomised trial.

BACKGROUND: A single co-administered dose of a triple-drug regimen (ivermectin, diethylcarbamazine, and albendazole) has been shown to be safe and more efficacious for clearing Wuchereria bancrofti microfilariae than the standard two-drug regimen of diethylcarbamazine plus albendazole in clinical trials. However, the effectiveness of mass drug administration with the triple-drug regimen compared with the two-drug regimen is unknown. We compared the effectiveness of mass drug administration with the triple-drug and two-drug regimens for reducing microfilariae prevalence to less than 1% and circulating filarial antigen prevalence to less than 2%, levels that are unlikely to sustain transmission of lymphatic filariasis, in Papua New Guinea. METHODS: This open-label, cluster-randomised study was done in 24 villages in a district endemic for lymphatic filariasis in Papua New Guinea. Villages paired by population size were randomly assigned to receive mass drug administration with a single dose of the triple-drug oral regimen of ivermectin (200 µg per kg of bodyweight) plus diethylcarbamazine (6 mg per kg of bodyweight) plus albendazole (400 mg) or a single dose of the two-drug oral regimen of diethylcarbamazine (6 mg per kg of bodyweight) plus albendazole (400 mg). This is a follow-on study of a previously reported safety study (ClinicalTrials.govNCT02899936). All residents aged 5 years or older and non-pregnant women were asked to participate. After cross-sectional night blood microfilariae and circulating filarial antigen surveys, mass drug administration was provided at baseline and repeated 12 months later. The primary outcomes were mean prevalence of microfilariae and circulating filarial antigen at 12 months and 24 months, assessed in all residents willing to participate at each timepoint. This study is registered with ClinicalTrials.gov, NCT03352206. FINDINGS: Between Nov 18, 2016, and May 26, 2017, 4563 individuals were enrolled in 24 clusters; 12 clusters (2382 participants) were assigned to the triple-drug regimen and 12 clusters (2181 participants) to the two-drug regimen. Mean drug ingestion rates (of residents aged ≥5 years) were 66·1% at baseline and 63·2% at 12 months in communities assigned to the triple-drug regimen and 65·9% at baseline and 54·9% at 12 months in communities assigned to the two-drug regimen. Microfilariae prevalence in the triple-drug regimen group decreased from 105 (4·4%) of 2382 participants (95% CI 3·6-5·3) at baseline to nine (0·4%) of 2319 (0·1-0·7) at 12 months and four (0·2%) of 2086 (0·1-0·5) at 24 months. In the two-drug regimen group, microfilariae prevalence decreased from 93 (4·3%) of 2181 participants (95% CI 3·5-5·2) at baseline to 29 (1·5%) of 1963 (1·0-2·1) at 12 months and eight (0·4%) of 1844 (0·2-0·9) at 24 months (adjusted estimated risk ratio 4·5, 95% CI 1·4-13·8, p=0·0087, at 12 months; 2·9, 95% CI 1·0-8·8, p=0·058, at 24 months). The prevalence of circulating filarial antigen decreased from 523 (22·0%) of 2382 participants (95% CI 20·3-23·6) at baseline to 378 (16·3%) of 2319 (14·9-17·9) at 12 months and 156 (7·5%) of 2086 (6·4-8·7) at 24 months in the triple-drug regimen group and from 489 (22·6%) of 2168 participants (20·7-24·2) at baseline to 358 (18·2%) of 1963 (16·7-20·1) at 12 months and 184 (10·0%) of 1840 (8·7-11·5) at 24 months in the two-drug regimen group; after adjustment, differences between groups were not significant. INTERPRETATION: Mass administration of the triple-drug regimen was more effective than the two-drug regimen in reducing microfilariae prevalence in communities to less than the target level of 1%, but did not reduce circulating filarial antigen prevalence to less than 2%. These results support the use of mass drug administration with the triple-drug regimen to accelerate elimination of lymphatic filariasis. FUNDING: Bill & Melinda Gates Foundation.

Downregulation of Dihydrotestosterone and Estradiol Levels by HEXIM1.

We have previously reported that hexamethylene bis-acetamide inducible protein 1 (HEXIM1) inhibits the activity of ligand-bound estrogen receptor α (ERα) and the androgen receptor (AR) by disrupting the interaction between these receptors and positive transcriptional elongation factor b (P-TEFb) and attenuating RNA polymerase II (RNAPII) phosphorylation at serine 2. Functional consequences of the inhibition of transcriptional activity of ERα and AR by HEXIM1 include the inhibition of ERα- and AR-dependent gene expression, respectively, and the resulting attenuation of breast cancer (BCa) and prostate cancer (PCa) cell proliferation and growth. In our present study, we determined that HEXIM1 inhibited AKR1C3 expression in BCa and PCa cells. AKR1C3, also known as 17ß-hydroxysteroid dehydrogenase (17ß-HSD) type 5, is a key enzyme involved in the synthesis of 17ß-estradiol (E2) and 5-dihydrotestosterone (DHT). Downregulation of AKR1C3 by HEXIM1 influenced E2 and DHT production, estrogen- and androgen-dependent gene expression, and cell proliferation. Our studies indicate that HEXIM1 has the unique ability to inhibit both the transcriptional activity of the ER and AR and the synthesis of the endogenous ligands of these receptors.

Recruitment strategies for a pragmatic cluster randomized oral health trial in pediatric primary care settings.

OBJECTIVES: To describe multilevel recruitment strategies for an ongoing clinical trial in pediatric primary care settings, and assess adoption and reach of these strategies via the RE-AIM framework. METHODS: This study is part of a larger pragmatic cluster randomized clinical trial focused on the effectiveness of interventions on the practice, provider, and caregiver levels on dental utilization for Medicaid-enrolled 3-6 year old children. Pediatric practices were recruited according to the proportion of Medicaid-eligible children, geographic region, and County. In accordance with the RE-AIM framework, providers reached were those approached directly and consented, and those who participated in the intervention training adopted to deliver the intervention. Caregivers reached were those approached and consented at their child's well-child visit to participate in the trial. RESULTS: Recruitment goals were met over a 21 month period, with an overall enrollment of 18 practices, 62 providers, and 1024 caregivers-child dyads. The majority of practices enrolled were small, suburban, and located in an urban county. The participation rates among approached providers and caregivers was 93% and 84% respectively. Enablers for recruitment was the one-on-one interaction with the provider and caregivers. Barriers to recruitment for caregivers included no-shows and cancellations at well-child visits. Adoption of intervention among providers was high, and caregiver reached were representative of the eligible target population. CONCLUSIONS: Active approaches to recruitment, such as utilizing opinion leaders, in-person recruitment, and building relationships with practice staff, can result in successful enrollment and imp lementation of a multi-level intervention in pediatric primary care settings.

Prenatal Substance Exposure and Developmental Trajectories of Internalizing Symptoms: Toddlerhood to Preadolescence.

BACKGROUND: Little is known about how prenatal exposure to substances (alcohol, tobacco, marijuana, and cocaine) may contribute to heterogeneous childhood trajectories of internalizing symptoms (i.e., depression, withdrawal, anxiety). The present study aimed to identify developmental trajectories of internalizing symptoms in children using gender-separate analyses and to examine whether trajectories differ by prenatal substance exposure (PSE) and other environmental and biological correlates. METHODS: Data from two large community-based birth cohorts with PSE were integrated (N = 1,651, 848 boys, 803 girls): the Cleveland cohort and the Maternal Lifestyle Study (MLS). Internalizing symptoms were assessed with the Child Behavior Checklist at ages 2, 4, 6, 9, 10, 11, and 12 in the Cleveland study and at ages 3, 5, 7, 9, 11, and 13 in the MLS. RESULTS: Gender-separate group-based trajectory modeling yielded five distinctive developmental trajectories of internalizing symptoms from ages 2 to 13 in both boys and girls: low-risk group (14.4% girls, 28.8% boys); normative-decreasing group (35.3% girls, 33.1% boys); increasing risk group (14.4% girls, 13.0% boys); early-high group (22.3% girls, 17.9% boys); and chronic group (13.8% girls, 7.2% boys). Prenatal tobacco exposure, maternal psychological distress, and postnatal maternal alcohol use differentiated the longitudinal courses of internalizing symptoms. Boys were more likely to follow the low-risk trajectory, whereas girls were more likely to follow the chronic trajectory. CONCLUSIONS: Prenatal tobacco exposure was associated with suboptimal developmental trajectories of internalizing symptoms in the context of prenatal poly-drug exposure, highlighting a need for continued and increased effort toward prevention of prenatal tobacco use.

Comparative Effectiveness of Two Nonsurgical Treatments to Reduce Oral Health Disparities From Untreated Tooth Decay in Older Adults: Protocol for a Cluster Randomized Trial.

BACKGROUND: The majority of dental caries lesions in older adults are at the gumline, at the edges of failed fillings and crowns, and in the surfaces of roots after gum recession. These lesions are difficult to restore with conventional surgical treatments using a dental drill and restorations often fail. Clinical guidelines are general and apply treatments that were designed for younger individuals in the dental care of older adults. OBJECTIVE: This study will compare the effectiveness of 2 evidence-based nonsurgical strategies to manage dental caries lesions in adults aged 62 or older: (1) biannual topical application of silver diamine fluoride versus (2) atraumatic restorative treatment + biannual fluoride varnish. METHODS: A cluster randomized clinical trial is being conducted in 22 publicly subsidized and other low-income housing facilities/sites (Arm 1: 11 sites, 275 participants; Arm 2: 11 sites, 275 participants). At baseline, participants will be screened for caries lesions. Those with nonurgent lesions will be treated according to the treatment arm to which the housing site was randomly assigned. The primary outcomes are caries lesion arrest, tooth sensitivity, and tooth pain at 52 weeks after treatment. Analytic methods for the primary aim include a generalized estimating equation approach to determine noninferiority of silver diamine fluoride relative to atraumatic restorative treatment + fluoride varnish treatment. RESULTS: The trial was funded in April 2019. Enrollment began in September 2019 and results are expected in June 2023. CONCLUSIONS: This study will inform the standard of care for treating caries lesions in older adults. If effective, either of these interventions has broad applicability in clinical and community-based settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT03916926; https://clinicaltrials.gov/ct2/show/NCT03916926. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/17840.