Objectives To estimate the prevalence of tooth wear and to investigate factors associated with tooth wear in patients from general practices in the Northwest United States. Methods Data on the diagnosis and treatment of oral diseases during the previous year were collected in a survey with a systematic random sample of patients (n = 1530) visiting general dentists from the Northwest Practice-based REsearch Collaborative in Evidence-based DENTistry (PRECEDENT) (n = 80). Prevalence ratios (PRs) of moderate to severe occlusal and incisal tooth wear by patient characteristics were estimated using cluster-adjusted multiple binomial regression for adults (18+ years) and children/adolescents (3–17 years). Results For adults, the mean number of teeth with wear facets was 5.4 [95% confidence interval (CI) = 4.6–6.2] and 51% of the adults had four or more teeth with wear. Participants 45–64 and 65+ years old were 1.3 (95% CI = 1.1–1.6) and 1.4 (95% CI = 1.1–1.8) times as likely to have 4+ teeth with moderate to severe wear facets as participants 18–44 years old. Adult males had a 20% (PR = 1.2; 95% CI = 1.1–1.4) higher prevalence of wear than adult females. Adults who were using, or had ever used occlusal splints had higher prevalence of tooth wear compared to those who never used such appliances (PR = 1.3; 95% CI = 1.0–1.5). Adults with any periodontal bone loss also had a 20% higher prevalence of wear than adults without periodontal disease (PR = 1.2; 95% CI = 1.0–1.4). For children/adolescents, the mean number of teeth with moderate to severe wear facets was 1.6 (95% CI = 0.9–2.6) and 31% of the children had one or more teeth with wear facets. The adjusted prevalence ratio of tooth wear (1+ teeth with wear facets) for boys was 1.6 times as high (95% CI = 1.1–2.4) as compared with girls. The prevalence of wear for children 12+ years old was 50% (PR = 0.5; 95% CI = 0.3–0.8) lower than that of children <12 years old. Angle’s class II was associated with higher tooth wear prevalence (PR = 1.8; 95% CI = 1.3–2.6) than class I. Children with posterior or anterior open bite had lower prevalence of wear than their counterparts (PR = 0.6; 95% CI = 0.3–1.0). No associations were observed between tooth wear and orthodontic treatment, missing teeth, and race/ethnicity. Conclusion Tooth wear is a prevalent condition in this population. Among adults, higher prevalences of tooth wear were observed among those who were older, males, had used occlusal splints and had periodontal disease. Among children, higher prevalences were associated with younger age, male gender, class II malocclusion and the absence of open bite. Submitted on behalf of the Northwest PRECEDENT network, with support from NIDCR grants DE016750 and DE016752.

Objectives This cross-sectional study by the Northwest PRECEDENT practitioners correlated the location of caries diagnosed in the past 12 months with treatment provided. Methods An oral health survey was conducted on up to 20 patients per practice for 101 practices in the Northwest PRECEDENT network. A total of 1943 eligible patients were randomly assessed for the location of and treatment provided for caries lesions diagnosed within the past 12 months. Regression analysis using Generalized Estimating Equations (GEE) was performed to assess association of treatment to tooth location and surface characterization, adjusting for age, practice location (urban/rural), dentist gender, and experience level. The analysis accounts for clustering by practice using robust variance estimates. Results Overall, 55.4% of patients exhibited recent caries and 42.8% received treatment for at least one permanent tooth. 18% of treated teeth were treated with amalgam, and 72% were treated with composite. This percentage varied as a function of tooth surface characteristics, patient characteristics, and dentist characteristics. The results suggest that restoration selection does depend on tooth type and which surfaces are being restored. The odds of a molar receiving an amalgam restoration are 2.44 (95% CI=1.81–3.30) times higher as compared to a bicuspid, adjusting for all other covariates. When the restoration includes the occlusal surface of a tooth the odds are 0.42 (95% CI=0.20–0.89) times as great that amalgam will be placed. When the restoration includes the mesial or distal surface of the tooth the odds for amalgam restoration are 2.49 (95% CI=1.25–4.95) times higher compared to when it does not include these surfaces. Conclusion Restorative material choice varied based on caries location and practitioner gender.

Purpose: Chemotherapy resistance remains a major problem in many solid tumors, including breast, ovarian, and pancreatic cancer. Glucocorticoids are one potential driver of chemotherapy resistance as they can mediate tumor progression via induction of cell-survival pathways. We investigated whether combining the selective glucocorticoid receptor modulator relacorilant with taxanes can enhance anti-tumor activity. Experimental Design: The effect of relacorilant on paclitaxel efficacy was assessed in OVCAR5 cells in vitro and in the MIA PaCa-2 xenograft. A phase 1 study of patients with advanced solid tumors was conducted to determine the recommended phase 2 dose of relacorilant + nab-paclitaxel. Results: In OVCAR5 cells, relacorilant reversed the deleterious effects of glucocorticoids on paclitaxel efficacy (P&lt;.001). Compared to paclitaxel alone, relacorilant+paclitaxel reduced tumor growth and slowed time to progression in xenograft models (both P&lt;.0001). In the heavily pretreated phase 1 population (median [range] of prior regimens: 3 [1-8], prior taxane in 75.3% [55/73]), 33% (19/57) of response-evaluable patients achieved durable disease control ({greater than or equal to}16 weeks) with relacorilant+nab-paclitaxel and 28.6% (12/42) experienced longer duration of benefit than on prior taxane (up to 6.4x). The most common dose-limiting toxicity of the combination was neutropenia, which was manageable with prophylactic granulocyte-colony stimulating factor. Clinical benefit with relacorilant+nab-paclitaxel was also associated with GR-regulated transcript-level changes in a panel of GR-controlled genes. Conclusions: Preclinical, clinical, and GR-specific pharmacodynamic responses observed demonstrate that selective GR modulation with relacorilant combined with nab-paclitaxel may promote chemotherapy response and is tolerable. Further evaluation of this combination in tumor types responsive to taxanes is ongoing.

In genetic association studies, it is typically thought that genetic variants and environmental variables jointly will explain more of the inheritance of a phenotype than either of these two components separately. Traditional methods to identify gene-environment interactions typically consider only one measured environmental variable at a time. However, in practice, multiple environmental factors may each be imprecise surrogates for the underlying physiological process that actually interacts with the genetic factors. In this paper we develop a variant of L2 boosting that is specifically designed to identify combinations of environmental variables that jointly modify the effect of a gene on a phenotype. Because the effect modifiers might have a small signal compared to the main effects, working in a space that is orthogonal to the main predictors allows us to focus on the interaction space. In a simulation study that investigates some plausible underlying model assumptions our method outperforms the lasso, and AIC and BIC model selection procedures as having the lowest test error. In an example for the WHI-PAGE study, the dedicated boosting method was able to pick out two single nucleotide polymorphisms for which effect modification appears present. The performance was evaluated on an independent test set and the results are promising.

PURPOSE Despite therapeutic advances, outcomes for patients with platinum-resistant/refractory ovarian cancer remain poor. Selective glucocorticoid receptor modulation with relacorilant may restore chemosensitivity and enhance chemotherapy efficacy. METHODS This three-arm, randomized, controlled, open-label phase II study (ClinicalTrials.gov identifier: NCT03776812 ) enrolled women with recurrent, platinum-resistant/refractory, high-grade serous or endometrioid epithelial ovarian, primary peritoneal, or fallopian tube cancer, or ovarian carcinosarcoma treated with ≤4 prior chemotherapeutic regimens. Patients were randomly assigned 1:1:1 to (1) nab-paclitaxel (80 mg/m2) + intermittent relacorilant (150 mg the day before, of, and after nab-paclitaxel); (2) nab-paclitaxel (80 mg/m2) + continuous relacorilant (100 mg once daily); or (3) nab-paclitaxel monotherapy (100 mg/m2). Nab-paclitaxel was administered on days 1, 8, and 15 of each 28-day cycle. The primary end point was progression-free survival (PFS) by investigator assessment; objective response rate (ORR), duration of response (DOR), overall survival (OS), and safety were secondary end points. RESULTS A total of 178 women were randomly assigned. Intermittent relacorilant + nab-paclitaxel improved PFS (hazard ratio [HR], 0.66; log-rank test P = .038; median follow-up, 11.1 months) and DOR (HR, 0.36; P = .006) versus nab-paclitaxel monotherapy, while ORR was similar across arms. At the preplanned OS analysis (median follow-up, 22.5 months), the OS HR was 0.67 ( P = .066) for the intermittent arm versus nab-paclitaxel monotherapy. Continuous relacorilant + nab-paclitaxel showed numerically improved median PFS but did not result in significant improvement over nab-paclitaxel monotherapy. Adverse events were comparable across study arms, with neutropenia, anemia, peripheral neuropathy, and fatigue/asthenia being the most common grade ≥3 adverse events. CONCLUSION Intermittent relacorilant + nab-paclitaxel improved PFS, DOR, and OS compared with nab-paclitaxel monotherapy. On the basis of protocol-prespecified Hochberg step-up multiplicity adjustment, the primary end point did not reach statistical significance ( P < .025). A phase III evaluation of this regimen is underway (ClinicalTrials.gov identifier: NCT05257408 ).