The Role of Pre-Existing Type 2 Diabetes Mellitus in Colorectal Cancer Stage and Survival in Elderly Americans: A Seer-Medicare Population-Based Study 2002-~2011

Diabetes is a common comorbid condition among colorectal cancer (CRC) patients, yet its effects in CRC outcomes, particularly stage at diagnosis, risk of death and variations by diabetes severity (complications vs no complications) and Hispanic ethnicity have not been adequately studied. The purpose of this study was to investigate the association between pre-existing T2DM and advanced stage at diagnosis in elderly patients with CRC; to examine whether diabetes is an independent predictor of poor survival from all-cause and CRC-specific mortality; to assess whether variations exist by diabetes severity and to analyze the outcomes for the Hispanic group. The Surveillance Epidemiology and End Results (SEER)-Medicare linked datasets were used to extract data on Medicare beneficiaries 67 years and older residing in the SEER areas who were diagnosed with CRC between 2002 and 2011. These datasets provided clinical, demographic, administrative claims and enrollment information for the Medicare population under study. Pre-existing T2DM was ascertained from the Medicare inpatient and outpatient claims using validated algorithms. The association of advanced stage at diagnosis with CRC was compared between pre-diabetic and non-diabetic patients using logistic regression. All-cause and CRC cause-specific death risk differences were compared using Cox proportional hazards model and hazard ratios were compared in relation to prior T2DM diagnosis and diabetes severity status. All models were adjusted for relevant factors including demographic characteristics such as age, sex, marital status, race/ethnicity and census poverty level. Clinical factors adjusted for included comorbidity score, grade, histology, stage at diagnosis, year of diagnosis and cancer registry. The analyses included 93,710 CRC patients. Among the study population, 22,155 (24%) had diabetes prior to CRC diagnosis and, of these, 17% had diabetes-related complications (neuropathy, nephropathy, retinopathy or peripheral circulatory disorders). Diabetic patients were more likely to be older, male, non-White, lived in medium to high poverty level areas, had at least one or more comorbidities, and had tumors in the proximal colon. From the regression models, diabetes was not significantly associated with CRC advanced stage at diagnosis (odds ratio (OR) = 0.986; 95% confidence interval (CI) = 0.953-1.02 for diabetes without complications and OR = 0.963; 95% CI = 0.897-1.034 for diabetes with complications). Similar results were observed for Hispanic patients. Overall mortality was significantly higher among diabetic patients compared to non-diabetic patients (hazard ratio (HR) = 1.198; 95% CI = 1.169-1.228). The results were more pronounced for diabetes with complications (HR = 1.467; 95% CI = 1.339-1.538). Patients who had diabetes with complications were 16% more likely to die of colorectal cancer compared to patients without diabetes in the fully adjust model (HR = 1.162; 95% CI = 1.083-1.247). Among Hispanics, diabetes was an independent predictor of poor survival from all-cause mortality but not CRC specific of death. This study used population-based data and the findings indicate that pre-existing diabetes contributes to poorer overall survival in patients with colorectal cancer and increased mortality from CRC in diabetes with complications. Because these diseases are more prevalent among the elderly, this group is more likely to have both diseases at the same time and more clinicians will need to develop care plans that are interdisciplinary and take into consideration the added burden of diabetes among CRC patients

The Effect of Marriage on Stage at Diagnosis and Survival in Women with Cervical Cancer

Marriage is associated with improved health outcomes for many conditions. Married persons enjoy financial stability, social and emotional support, and tend to have better control of health risk behaviors compared to the unmarried. The marriage scene is changing continuously. Americans are marrying less or delaying the engagement to an older age. They are divorcing more, they choose cohabitation as an alternative to marriage, or engage in premarital relationships. As a consequence, barely half of Americans were married in 2011 compared to close to three quarters of Americans were married in the sixties. With the increase of the unmarried population - including those who cohabitate, the never married, the divorced, and the widowed - understanding whether marriage is an independent determinant of health outcomes is an important public health matter. The relationship of marriage and health outcomes has been studied for many health conditions and cancer sites. However, this association has not been fully explored for cervical cancer outcomes. In addition, studies with recent data are lacking. This study aimed at investigating whether marriage has a protective effect from late stage of diagnosis and whether it independently improves survival in women with cervical cancer with more recent population-based data. The National Cancer Institute program Surveillance, Epidemiology, and End Results (SEER) was used to identify women with cervical cancer diagnosed between 2000 and 2010. Statistical analyses were conducted to assess the effect of marriage on stage and survival. The Logistic regression modeling was used to calculate the odds ratios of advanced stage - defined as regional and distant - accounting for socio-demographic and clinical covariates. Hazard ratios were obtained by the Cox Proportional Hazards modeling to compare death risk between married and unmarried women. Additional modeling was conducted with cases diagnosed between 2007 and 2010 to account for insurance status at diagnosis. Kaplan Meier survival curves and Log Rank test of difference in survival between marital groups were executed. Interactions between marital status and age; between marital status and race; and between marital status and stage were tested. In terms of stage of diagnosis, Single [adjusted odds ratio (aOR) 1.41; 95% CI = 1.33-1.49], separated/divorced [aOR 1.44; 95% CI = 1.34-1.55], and widowed women [aOR 1.43; 95% CI = 1.31-1.58] were significantly more likely to be diagnosed at an advanced stage compared to married women after controlling for age, race/ethnicity, period of diagnosis, histology, and SEER area. Marital status was found to be an independent factor for survival. Single (aHR 1.35; 95% CI = 1.28-1.43), separated (aHR 1.22; 95% CI = 1.15-1.29), and widowed women (aHR 1.28; 95% CI = 1.19-1.36) had increased death risk compared to married women adjusted for socio-demographic (age, race/ ethnicity) and clinical factors (stage, histology, and period of diagnosis). Even after controlling for insurance status, married women continued to be more likely to be diagnosed early and have favorable survival over the unmarried. Findings from this study support the rising body of literature of the protective effect of marriage on cancer outcomes. Particularly for cervical cancer, based on its sexually transmitted etiology, unmarried women are more likely to have multiple sexual partners and are, therefore, at increased risk of developing this cancer. Moreover, unmarried women are more likely to have inadequate access to health care, which reduces their chance of receiving recommended cervical screening services and timely treatment. In addition, unmarried women lack spousal emotional and social support, which contribute to psychosocial stress and unfavorable health outcomes. National guidelines on cervical cancer risk factors may need to be revised to include marital status as an independent predictor for stage of diagnosis and survival. Further qualitative and quantitative research is needed to determine how to improve health outcomes for the unmarried population in the clinical and the community settings

Factors Associated with Opioid Overdose after an Initial Opioid Prescription

Importance: The opioid epidemic continues to be a public health crisis in the US. Objective: To assess the patient factors and early time-varying prescription-related factors associated with opioid-related fatal or nonfatal overdose. Design, Setting, and Participants: This cohort study evaluated opioid-naive adult patients in Oregon using data from the Oregon Comprehensive Opioid Risk Registry, which links all payer claims data to other health data sets in the state of Oregon. The observational, population-based sample filled a first (index) opioid prescription in 2015 and was followed up until December 31, 2018. Data analyses were performed from March 1, 2020, to June 15, 2021. Exposures: Overdose after the index opioid prescription. Main Outcomes and Measures: The outcome was an overdose event. The sample was followed up to identify fatal or nonfatal opioid overdoses. Patient and prescription characteristics were identified. Prescription characteristics in the first 6 months after the index prescription were modeled as cumulative, time-dependent measures that were updated monthly through the sixth month of follow-up. A time-dependent Cox proportional hazards regression model was used to assess patient and prescription characteristics that were associated with an increased risk for overdose events. Results: The cohort comprised 236921 patients (133 839 women [56.5%]), of whom 667 (0.3%) experienced opioid overdose. Risk of overdose was highest among individuals 75 years or older (adjusted hazard ratio [aHR], 3.22; 95% CI, 1.94-5.36) compared with those aged 35 to 44 years; men (aHR, 1.29; 95% CI, 1.10-1.51); those who were dually eligible for Medicaid and Medicare Advantage (aHR, 4.37; 95% CI, 3.09-6.18), had Medicaid (aHR, 3.77; 95% CI, 2.97-4.80), or had Medicare Advantage (aHR, 2.18; 95% CI, 1.44-3.31) compared with those with commercial insurance; those with comorbid substance use disorder (aHR, 2.74; 95% CI, 2.15-3.50), with depression (aHR, 1.26; 95% CI, 1.03-1.55), or with 1 to 2 comorbidities (aHR, 1.32; 95% CI, 1.08-1.62) or 3 or more comorbidities (aHR, 1.90; 95% CI, 1.42-2.53) compared with none. Patients were at an increased overdose risk if they filled oxycodone (aHR, 1.70; 95% CI, 1.04-2.77) or tramadol (aHR, 2.80; 95% CI, 1.34-5.84) compared with codeine; used benzodiazepines (aHR, 1.06; 95% CI, 1.01-1.11); used concurrent opioids and benzodiazepines (aHR, 2.11; 95% CI, 1.70-2.62); or filled opioids from 3 or more pharmacies over 6 months (aHR, 1.38; 95% CI, 1.09-1.75). Conclusions and Relevance: This cohort study used a comprehensive data set to identify patient and prescription-related risk factors that were associated with opioid overdose. These findings may guide opioid counseling and monitoring, the development of clinical decision-making tools, and opioid prevention and treatment resources for individuals who are at greatest risk for opioid overdose

Association between “cluster of differentiation 36 (CD36)” and adipose tissue lipolysis during exercise training: a systematic review

Fatty acid translocase (FAT/CD36) is a transmembrane glycoprotein belonging to the scavenger class B receptor family and is encoded by the cluster of differentiation 36 (CD36) gene. This receptor has a high affinity for fatty acids and is involved in lipid metabolism. An abundance of FAT/CD36 during exercise occurs in mitochondria and solitary muscles. As such, we aimed to systematically review the evidence for the relationship FAT/CD36 and adipose tissue lipolysis during exercise training. Five electronic databases were selected for literature searches until June 2022: PubMed, Web of Science, Scopus, science direct, and Google Scholar. We combined the different synonyms and used the operators (“AND”, “OR”, “NOT”): (CD36 gene) OR (CD36 polymorphism) OR (cluster of differentiation 36) OR (FAT/CD36) OR (fatty acid translocase) OR (platelet glycoprotein IV) OR (platelet glycoprotein IIIb) AND (adipose tissue lipolysis) OR (fatty acids) OR (metabolism lipid) OR (adipocytes) AND (physical effort) OR (endurance exercise) OR (high-intensity training). All published cross-sectional, cohort, case-control, and randomized clinical trials investigating CD36 polymorphisms and adipose tissue lipolysis during exercise in subjects (elite and sub-elite athletes, non-athletes, sedentary individuals and diabetics), and using valid methods to measure FAT/CD36 expression and other biomarkers, were considered for inclusion in this review. We initially identified 476 publications according to the inclusion and exclusion criteria, and included 21 studies investigating FAT/CD36 and adipose tissue lipolysis during exercise in our systematic review after examination of titles, abstracts, full texts, and quality assessments using the PEDro scale. There were nine studies with male-only participants, three with female-only participants, and nine studies included both female and male participants. There were 859 participants in the 21 selected studies. Studies were classified as either low quality (n = 3), medium quality (n = 13), and high quality (n = 5). In general, the data suggests an association between FAT/CD36 and adipose tissue lipolysis during exercise training. Improvements in FAT/CD36 were reported during or after exercise in 6 studies, while there were no changes reported in FAT/CD36 in 4 studies. An association between fat oxidation and FAT/CD36 expression during exercise was reported in 7 studies. No agreement was reached in 5 studies on FAT/CD36 content after dietary changes and physical interventions. One study reported that FAT/CD36 protein expression in muscle was higher in women than in men, another reported that training decreased FAT/CD36 protein in insulin-resistant participants, while another study reported no differences in FAT/CD36 in young, trained individuals with type 2 diabetes. Our analysis shows an association between FAT/CD36 expression and exercise. Furthermore, an association between whole-body peak fat oxidation and FAT/CD36 expression during exercise training was demonstrated.Systematic Review Registration: [PROSPERO], identifier [CRD42022342455

C- versus O-Arylation of an Enol-Lactone Using Potassium tert-butoxide

The use of potassium tert-butoxide as the base in arylation reactions of an enollactone with a series of benzyl halides was explored. Our work demonstrates that the ratio of C-arylation to O-arylation varies with the substitution pattern of the aryl halide

www.mdpi.org/ijms/ C- versus O-Arylation of an Enol-Lactone Using Potassium tertbutoxide

Abstract: The use of potassium tert-butoxide as the base in arylation reactions of an enollactone with a series of benzyl halides was explored. Our work demonstrates that the ratio of C-arylation to O-arylation varies with the substitution pattern of the aryl halide

Effects of Malocclusion on Maximal Aerobic Capacity and Athletic Performance in Young Sub-Elite Athletes

International audienceOral pathologies can cause athletic underperformance. The aim of this study was to determine the effect of malocclusion on maximal aerobic capacity in young athletes with the same anthropometric data, diet, training mode, and intensity from the same athletics training center. Sub-elite track and field athletes (middle-distance runners) with malocclusion (experimental group (EG); n = 37; 21 girls; age: 15.1 ± 1.5 years) and without malocclusion (control group (CG); n = 13; 5 girls; age: 14.7 ± 1.9 years) volunteered to participate in this study. Participants received an oral diagnosis to examine malocclusion, which was defined as an overlapping of teeth that resulted in impaired contact between the teeth of the mandible and the teeth of the upper jaw. Maximal aerobic capacity was assessed using the VAMEVAL test (calculated MAS and estimated VO(2max)). The test consisted of baseline values that included the following parameters: maximum aerobic speed (MAS), maximal oxygen uptake (VO(2max)), heart rate frequency, systolic (SAP) and diastolic arterial pressure (DAP), blood lactate concentration (LBP), and post-exercise blood lactate assessment (LAP) after the performance of the VAMEVAL test. There were no statistically significant differences between the two study groups related to either anthropometric data (age: EG = 15.1 ± 1.5 vs. CC = 14.7 ± 1.9 years (p = 0.46); BMI: EG = 19.25 ± 1.9 vs. CC = 19.42 ± 1.7 kg/m(2) (p = 0.76)) or for the following physical fitness parameters and biomarkers: MAS: EG = 15.5 (14.5-16.5) vs. CG = 15.5 (15-17) km/h (p = 0.47); VO(2max): EG = 54.2 (52.5-58.6) vs. CG = 54.2 (53.4-59.5) mL/kg/min (p = 0.62) (IQR (Q1-Q3)); heart rate before the physical test: EG = 77.1 ± 9.9 vs. CG = 74.3 ± 14.0 bpm (p = 0.43); SAP: EG = 106.6 ± 13.4 vs. CG = 106.2 ± 14.8 mmHg (p = 0.91); DAP: EG = 66.7 ± 9.1 vs. CG = 63.9 ± 10.2 mmHg (p = 0.36); LBP: EG = 1.5 ± 0.4 vs. CG = 1.3 ± 0.4 mmol/L (p = 0.12); and LAP: EG = 4.5 ± 2.36 vs. CG = 4.06 ± 3.04 mmol/L (p = 0.60). Our study suggests that dental malocclusion does not impede maximal aerobic capacity and the athletic performance of young track and field athletes

Association of household opioid availability with opioid overdose.

Importance: Previous studies that examined the role of household opioid prescriptions in opioid overdose risk were limited to commercial claims, did not include fatal overdoses, and had limited inclusion of household prescription characteristics. Broader research is needed to expand understanding of the risk of overdose. Question: What role do household opioid prescription availability and prescription characteristics play in an individual’s odds of opioid overdose? Findings: In this cohort study of 1 691 856 Oregon adults in 1 187 140 households, the odds of opioid-related overdose increased significantly when another household member had opioid fills in the preceding 6 months. The odds also increased when both the individual and another household member had opioid fills in the preceding 6 months. Meaning: The findings of this cohort study underscore the importance of educating individuals about the risks of keeping opioids in the household