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.

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.

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.

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.

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.

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.

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.

Toll-like receptor distribution in colonic epithelium and lamina propria is disrupted in HIV viremic, immune success, and failure.

DESIGN: Since intestinal immunity and the microbiome are disrupted in HIV disease, we studied the abundance of innate immune sensors, Toll-like receptors (TLRs), in the mucosa of participants with viremia, prior to antiretroviral therapy (ART), immune success (>500 CD4 T cells/µl after 2 years of ART; suppressed viremia), and immune failure (<350 CD4 T cells/µl after 2 years of ART; suppressed viremia). We hypothesized that disruption of intestinal TLR abundance and location provides a mechanism behind persistent inflammation. METHODS: Immunofluorescence for TLR3, TLR4, and TLR9 on paraffin embedded biopsies from uninfected, viremic, immune success, and immune failure colons was imaged by deconvolution microscopy and quantified with MetaMorph software. Plasma levels of C-reactive protein, IL-6, and intestinal fatty-acid binding protein (I-FABP) were correlated with TLR expression. RESULTS: Viremic participants have significantly higher levels of TLR3 and TLR9 on surface epithelium and in crypts when compared with uninfected controls. TLR3 is further elevated in immune failure and immune success. TLR9 abundance remains elevated in immune failure and is normalized in immune success. TLR9 expression in the crypt and lamina propria positively associates with C-reactive protein and IL-6 and negatively with I-FABP. TLR4 is significantly lower on surface epithelium and higher in crypts in viremic. Its expression in the lamina propria positively correlates with IL-6 and negatively correlates with I-FABP. CONCLUSION: Mucosal TLR imbalance and deregulation, and the resulting mucosal TLR desensitization and hypervigilance, remain after suppressive ART, in the presence or absence of T-cell recovery, likely contributing to chronic systemic inflammation.

Gendered "Long Arm" of Parental Education? Life Course Influences on Later Life Functional Limitations in India.

Objective: We adopt a novel approach to mediation analysis to account for interrelated life course social processes that constitute later life health disparities. We examine gender-specific direct effect of parental education on functional limitations in later life. Method: Based on the first wave (2007-2010; n = 7,150) of the Study on Global Ageing and Adult Health (SAGE), we estimate both (natural) direct and indirect effects of parental education on functional limitations in later life. Results: We observed a significant indirect and positive effect of parental education on functional health. Contrary to prior literature, we documented adverse direct effect of parental education on later life functional health. The direct effect is statistically significant only for father's education, and is greater, though not statistically significantly so, for women than men. Discussion: The intersection of gender status and interrelated social stratification documented by this study highlights the need for gender-sensitive life course research. Such research can enhance our understanding of the ways patriarchal social systems produce heterogeneous effects of interrelated structural factors on later life health for men and women.

Continuous Time Nonstationary Correlation Models for Sparse Longitudinal Data.

In this paper, we present a new continuous time model for nonstationary correlation structures for longitudinal data. This model, which provides a continuous time analogue to the antedependence model and is thus referred to as the continuous antedependence (CAD) model, is intended to provide more refined correlation models for longitudinal data and to better accommodate sparse (or highly unbalanced) data. A key component of this model is the 'nonstationarity function' which describes nonstationarity as a unidimensional function of time and has an interesting time expansion/contraction interpretation. Focusing on a Markovian version of the model, we develop a novel nonlinear regression model providing nonlinear least square estimators of model parameters. Both unstructured (for nonparametric estimation) and structured versions of the model are presented. We apply the proposed approach to data from the Multicenter AIDS Clinical Study (MACS), with a focus on inference for the nonstationarity function. In simulation studies, we show good properties (low finite sample bias, and high convergence rates and efficiency) of the proposed unstructured model estimator, which compare favorably to those of an alternative maximum likelihood estimator, particularly in sparse data situations.

Continuous-time causal mediation analysis.

While causal mediation analysis has seen considerable recent development for a single measured mediator (M) and final outcome (Y), less attention has been given to repeatedly measured M and Y. Previous methods have typically involved discrete-time models that limit inference to the particular measurement times used and do not recognize the continuous nature of the mediation process over time. To overcome such limitations, we present a new continuous-time approach to causal mediation analysis that uses a differential equations model in a potential outcomes framework to describe the causal relationships among model variables over time. A connection between the differential equation models and standard repeated measures models is made to provide convenient model formulation and fitting. A continuous-time extension of the sequential ignorability assumption allows for identifiable natural direct and indirect effects as functions of time, with estimation based on a two-step approach to model fitting in conjunction with a continuous-time mediation formula. Novel features include a measure of an overall mediation effect based on the "area between the curves," and an approach for predicting the effects of new interventions. Simulation studies show good properties of estimators and the new methodology is applied to data from a cohort study to investigate sugary drink consumption as a mediator of the effect of socioeconomic status on dental caries in children.

Plasma Cystatin C Associates With HIV-Associated Neurocognitive Disorder but Is a Poor Diagnostic Marker in Antiretroviral Therapy-Treated Individuals.

OBJECTIVE: To examine associations between plasma cystatin C and neurocognitive impairment (NCI) and its performance as a diagnostic marker before and during initial antiretroviral therapy (ART). METHODS: Multivariable logistic regression and generalized estimating equations examined associations with NCI, determined by neuropsychological measurements, in participants of a 48-week randomized clinical trial of initial ART. Receiver operator characteristic curves examined diagnostic models of NCI. RESULTS: Cystatin C was associated with NCI before ART [odds ratio (OR) 3.4 (95% CI: 1.2 to 9.4) for each 2-fold increase in baseline levels] and during 48 weeks of ART, in models that excluded baseline measurements [OR 3.0 (1.2 to 7.8) for each 2-fold increase in time-updated levels]. The strength of association increased with more severe impairment using HIV-associated neurocognitive disorder criteria [OR 2.2 (0.8 to 6.0) with asymptomatic NCI and OR 4.0 (1.5 to 11.0) with mild neurocognitive disorder or HIV-associated dementia vs. no impairment, for each 2-fold increase in time-updated levels] or by global development score [OR 2.6 (1.1 to 6.3) with mild impairment and OR 4.6 (1.1 to 18.9) with moderate or severe impairment vs. no impairment]. Cystatin C performed poorly as a diagnostic marker for NCI, however, with an area under the receiver operator characteristic curve of 0.58 at baseline and 0.54 at week 48. CONCLUSIONS: Higher plasma cystatin C levels were significantly associated with NCI, but these levels did not seem to be useful as a diagnostic marker for this condition.

The psychometric properties of a new oral health illness perception measure for adults aged 62 years and older.

BACKGROUND: Based on the Common-Sense Model of Self-Regulation (CSM), a new integrated Illness Perception Questionnaire Revised for Dental Use in Older/Elder Adults (IPQ-RDE) was developed for single and multiple dental conditions. This study describes psychometric properties of the IPQ-RDE for adults 62 years and older. METHODS: Participants (n = 198) living in 16 subsidized housing facilities completed the IPQ-RDE and a questionnaire assessing their socio-demographics, frequency of dental visits, perceived condition of teeth/gums, depression, social support, and oral health quality of life (OHQOL). Participants received dental screening for presence/absence of teeth, coronal and root caries, and periodontitis. The 43-item IPQ-RDE was tested for internal (construct, discriminant) and external validity (concurrent, construct, discriminant, predictive) and reliability (internal consistency). RESULTS: Confirmatory factor analysis demonstrated that a ten-factor model in accordance with the CSM framework (identity, consequences, control, timeline, illness coherence, treatment burden, prioritization, causal relationship, activity restriction, emotional representations) had good construct validity based on significant factor loadings and acceptable model fit (RMSEA = 0.065, CFI = 0.902). Edentulous participants had significantly higher mean factor scores (inaccurate perception) for overall IPQ-RDE and four constructs indicating concurrent validity. Discriminant validity was suggested by non-relationship with external measures (education, dental visit frequency). Predictive validity was indicated by the negative correlation of most constructs with OHQOL suggesting that inaccurate perception was related to lower quality of life. Internal consistency of eight IPQ-RDE constructs was excellent (Cronbach's alpha > 0.73). CONCLUSIONS: The IPQ-RDE is a valid and reliable new measure for assessing older adult's perception of dental conditions. It can be an important tool for oral health behavioral research to restructure older adult's perception of dental conditions, and subsequently prevent tooth loss and improve oral health quality of life.

Comparing web-based video interventions to enhance university student willingness to donate organs: A randomized controlled trial.

BACKGROUND: The efficacy of video interventions to increase organ donation willingness remains unclear. METHODS: Three-arm web-based randomized controlled trial involving 2261 students at 3 northeastern Ohio universities. Intervention students watched a live-action (n = 755) or animated (n = 753) donation video. Control students (n = 753) viewed wellness information from the Centers for Disease Control and Prevention (CDC). The primary outcome was proportion of students who visited their state electronic donor registry to consent. The secondary outcome was intervention quality. Logistic regression assessed the effects of interventions on visiting the state registry to provide donation consent while controlling for baseline variables. RESULTS: Students in the live-action video arm visited their state registry more frequently than students in the CDC arm (OR = 1.86, 95% CI = 1.20-2.88). There was no difference between students in the animated video and CDC arms (OR = 1.10, 95% CI = 0.69-1.76). The quality of the live-action video was rated lower than the animated video and the CDC text (75% ± 18, 84% ± 16, 80% ± 16, respectively; P < 0.001). CONCLUSION: Students who watched the live-action video were more willing to visit their electronic donor registry to register as organ donors, but rated it lower in satisfaction. Future work should identify the most potent components of organ donation interventions.