Subjective Oral Dryness following Hematopoietic Cell Transplantation: A Report from the Orastem Study.

Xerostomia, or subjective oral dryness, is a serious complaint after hematopoietic cell transplantation (HCT). Xerostomia is rated as one of the most bothersome symptoms by HCT recipients, negatively affecting quality of life. This substudy of the Orastem study, a prospective longitudinal, international, observational, multicenter study, aimed to describe the prevalence and severity of xerostomia following HCT. Furthermore, the effect of the conditioning regimen, type of transplantation, and oral mucosal changes related to chronic graft-versus-host disease (cGVHD) in the development of xerostomia were studied. All HCT recipients rated xerostomia on a scale of 0 to 10 before the conditioning regimen, several times early post-HCT, and at 3 months post-HCT, and only allogeneic HCT recipients also rated xerostomia at 6 and 12 months post-HCT. In addition, stimulated whole mouth saliva was collected several times. Linear regression models and longitudinal mixed-effects models were created to investigate the influence of risk indicators on xerostomia. A total of 99 autologous and 163 allogeneic HCT recipients were included from 6 study sites in Sweden, Canada, the Netherlands, and the United States. The prevalence of xerostomia was 40% before the conditioning regimen, 87% early post-HCT, and 64% at 3 months post-HCT. Complaints after autologous HCT were transient in nature, while the severity of xerostomia in allogeneic HCT recipients remained elevated at 12 months post-HCT. Compared to autologous HCT recipients, allogeneic HCT recipients experienced 1.0 point more xerostomia (95% confidence interval [CI], .1 to 2.0) early post-HCT and 1.7 points more (95% CI, .4 to 3.0) at 3 months post-HCT. Allogeneic HCT recipients receiving a high-intensity conditioning regimen experienced more xerostomia compared to those receiving a nonmyeloablative or reduced-intensity conditioning regimen. The difference was 2.0 points (95% CI, 1.1 to 2.9) early post-HCT, 1.8 points (95% CI, .3 to 3.3) after 3 months, and 1.7 points (95% CI, .0 to 3.3) after 12 months. Total body irradiation as part of the conditioning regimen and oral mucosal changes related to cGVHD did not significantly influence the severity of xerostomia. Conditioning regimen intensity was a significant risk indicator in the development of xerostomia, whereas total body irradiation was not. Allogeneic HCT recipients experienced more xerostomia than autologous HCT recipients, a difference that cannot be explained by a reduction in stimulated salivary flow rate or the development of oral mucosal changes related to cGVHD.

Lenalidomide in the treatment of anti-myelin-associated glycoprotein neuropathy: A phase 1 study to identify the maximum tolerated dose.

BACKGROUND: Anti-myelin-associated glycoprotein (MAG) neuropathy is a debilitating demyelinating polyneuropathy with no approved therapies. Our primary objective was to ascertain lenalidomide safety and maximum tolerated dose (MTD) in anti-MAG neuropathy. METHODS: This phase 1b, open-label, single-arm, dose-finding trial was conducted from 2019 through 2022. The original design included a dose-escalation/extension phase followed by a dose-expansion phase. Three doses of lenalidomide were evaluated: 10, 15, and 25 mg. The main outcome was the MTD. RESULTS: Eleven patients enrolled (10 men), with a mean age of 67.6 years (SD = 6.18, range 58-77 years) and mean disease duration of 8.5 years (SD = 10.9, range 1-40 years). The study terminated early due to higher-than-expected non-dose-limiting toxicity venous thromboembolism (VTE) events. The calculated MTD was 25 mg (posterior mean of toxicity probability was 0.01 with a 95% credible interval of 0.00, 0.06), but a recommended phase 2 dose of 15 mg was advised. For secondary exploratory outcomes, only EQ-5D (-0.95, 95% CI -1.81 to -0.09) and total IgM (-162 mg/dL, 95% CI -298 to -26) showed signs of improvement by month 12. CONCLUSIONS: Lenalidomide was associated with higher-than-expected VTE events in anti-MAG neuropathy patients, despite a calculated MTD of 25 mg. A recommended phase 2 dose of 15 mg was advised. Lenalidomide did not improve disability or impairment at 12 months, although this study was not powered for efficacy. The risks of long term lenalidomide may outweigh benefit for patients with anti-MAG neuropathy. Any future efficacy study should address VTE risk, as current myeloma guidelines appear inadequate. TRIAL REGISTRATION: Lenalidomide in Anti-MAG Neuropathy: Phase 1b Study, ClinicalTrials.gov Identifier: NCT03701711, https://clinicaltrials.gov/ct2/show/NCT03701711. First submitted October 10, 2018. First patient enrolled in January 2019.

Geographic Variation in Operative Management of Adhesive Small Bowel Obstruction.

INTRODUCTION: Variation in surgical management exists nationally. We hypothesize that geographic variation exists in adhesive small bowel obstruction (aSBO) management. MATERIALS AND METHODS: A retrospective analysis of a national commercial insurance claims database (MarketScan) sample (2017-2019) was performed in adults with hospital admission due to aSBO. Geographic variation in rates of surgical intervention for aSBO was evaluated by state and compared to a risk-adjusted national baseline using a Bayesian spatial rates Poisson regression model. For individual-level analysis, patients were identified in 2018, with 365-d look back and follow-up periods. Logistic regression was performed for individual-level predictors of operative intervention for aSBO. RESULTS: Two thousand one hundred forty-five patients were included. State-level analysis revealed rates of operative intervention for aSBO were significantly higher in Missouri and lower in Florida. On individual-level analysis, age (P < 0.01) and male sex (P < 0.03) but not comorbidity profile or prior aSBO, were negatively associated with undergoing operative management for aSBO. Patients presenting in 2018 with a history of admission for aSBO the year prior experienced a five-fold increase in odds of representation (odds ratio: 5.4, 95% confidence interval: 3.1-9.6) in 2019. Patients who received an operation for aSBO in 2018 reduced the odds of readmission in the next year by 77% (odds ratio: 0.23, 95% confidence interval: 0.1-0.5). The volume of operations performed within a state did not influence readmission. CONCLUSIONS: Surgical management of aSBO varies across the continental USA. Operative intervention is associated with decreased rates of representation in the following year. These data highlight a critical need for standardized guidelines for emergency general surgery patients.

Childhood environment early life stress, caregiver warmth, and associations with the cortisol diurnal curve in adulthood: The coronary artery risk development in young adults (CARDIA) study.

BACKGROUND: Early life stress (ELS) is associated with increased morbidity and mortality across the lifecourse. Studies observing a relationship between ELS and stress physiology (cortisol), may help explain the connection to poor health outcomes, but have been limited by cortisol measures used. PURPOSE: We examined the association between ELS measured by a Risky Family (RF) environment questionnaire, and adult diurnal cortisol profile inclusive of multiple cortisol measures. METHODS: RF and cortisol were collected from Coronary Artery Risk Development in Young Adults Study participants at follow-up (Year 15). Complete case (n = 672) data were included in multi-variable regression analyses with log transformed cortisol measures (outcomes) including wake-up cortisol, cortisol awakening response [CAR], AUC and five other cortisol diurnal curve measures. RESULTS: Participants were age 39.9 + /- 3.7 years and 51.6% Black. For every 1 unit increase in RF, there was a 1.4% greater wake-up cortisol and flatter CAR after adjustment for age, sex, income, and smoking (B=0.014, p = 0.023; B=-0.014, p = 0.028, respectively). Each unit increase in caregiver warmth/affection was associated with a 6.9% higher (steeper) CAR (B=0.069, p = 0.03). Results remained significant after adjusting for other covariates except social support in adulthood. An interaction between child abuse and caregiver warmth was nearly significant (p = 0.068), such that for those with exposure to the greatest caregiver warmth and lowest child abuse, CAR was steepest CONCLUSIONS: We demonstrate that ELS is associated with altered cortisol regulation in adulthood. However, further research is needed to assess how healthy relationships throughout the life course may modulate cortisol regulation in adulthood.

Association Between Social Determinants of Health and Glycemic Control Among African American People with Type 2 diabetes: The Jackson Heart Study.

BACKGROUND: Social determinants of health have a significant impact on health outcomes. However, the complexity and interaction of multiple factors influencing glycemic control remain understudied. PURPOSE: This study examined associations of socioeconomic position (income, education, and occupation), environmental (physical activity facilities, neighborhood social cohesion, neighborhood problem, and violence), behavioral (physical activity, nutrition, and smoking), and psychological factors (depressive symptoms, stress, and discrimination) with glycemic control (hemoglobin A1c [A1c]) using the World Health Organization Social Determinants of Health framework in African American adults with type 2 diabetes. METHODS: A secondary data analysis was conducted using a longitudinal cohort of 1,240 African American adults with type 2 diabetes who participated in the community-based Jackson Heart Study. Socioeconomic position, environmental, behavioral, and psychological factors were measured using validated instruments in the Jackson Heart Study. Longitudinal structural equation modeling was used with glycemic control (A1c) collected over time (Exams 1-3) as the study outcome. RESULTS: Our study presents the complex interplay of socioeconomic determinants of health and glycemic control over time. Higher socioeconomic position (higher income, higher level of education, and professional occupation) was directly associated with improvement in glycemic control over time. An association of socioeconomic position on glycemic control mediated through health behavior factors was also observed. CONCLUSIONS: In this analysis, socioeconomic position components were determinants of glycemic control in African American adults with type 2 diabetes. Future studies aimed at reducing health disparities and achieving equality of outcomes in this population will benefit from embedding socioeconomic position components into their design.