A non-invasive 25-Gene PLNM-Score urine test for detection of prostate cancer pelvic lymph node metastasis.

BACKGROUND: Prostate cancer patients with pelvic lymph node metastasis (PLNM) have poor prognosis. Based on EAU guidelines, patients with >5% risk of PLNM by nomograms often receive pelvic lymph node dissection (PLND) during prostatectomy. However, nomograms have limited accuracy, so large numbers of false positive patients receive unnecessary surgery with potentially serious side effects. It is important to accurately identify PLNM, yet current tests, including imaging tools are inaccurate. Therefore, we intended to develop a gene expression-based algorithm for detecting PLNM. METHODS: An advanced random forest machine learning algorithm screening was conducted to develop a classifier for identifying PLNM using urine samples collected from a multi-center retrospective cohort (n = 413) as training set and validated in an independent multi-center prospective cohort (n = 243). Univariate and multivariate discriminant analyses were performed to measure the ability of the algorithm classifier to detect PLNM and compare it with the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram score. RESULTS: An algorithm named 25 G PLNM-Score was developed and found to accurately distinguish PLNM and non-PLNM with AUC of 0.93 (95% CI: 0.85-1.01) and 0.93 (95% CI: 0.87-0.99) in the retrospective and prospective urine cohorts respectively. Kaplan-Meier plots showed large and significant difference in biochemical recurrence-free survival and distant metastasis-free survival in the patients stratified by the 25 G PLNM-Score (log rank P < 0.001 and P < 0.0001, respectively). It spared 96% and 80% of unnecessary PLND with only 0.51% and 1% of PLNM missing in the retrospective and prospective cohorts respectively. In contrast, the MSKCC score only spared 15% of PLND with 0% of PLNM missing. CONCLUSIONS: The novel 25 G PLNM-Score is the first highly accurate and non-invasive machine learning algorithm-based urine test to identify PLNM before PLND, with potential clinical benefits of avoiding unnecessary PLND and improving treatment decision-making.

Educating Family Physician Residents for Anesthetic Preoperative Evaluation and Assessment.

Introduction: Encounters for preoperative assessments are common within primary care offices, so it is imperative that family medicine residents learn how to perform preoperative evaluations. We assessed family medicine residents' knowledge of preoperative evaluation in preparation for surgery by providing a pre- and post-test alongside a didactic seminar. Methods: A didactic seminar on preoperative evaluations was presented at a family medicine resident didactics session by two senior anesthesiology residents. A 16-question, multiple choice test was used as both a pre-test and post-test to assess family medicine residents' knowledge. Results: A total of 31 participants took the pre-test (residents = 24; medical students = 7), and 30 participants took the post-test (residents = 23; medical students = 7). Mean scores and standard deviations were calculated for both tests with an average score of 37.50% ± 10.58% and 45.42% ± 11.12% on the pre- and post-test, respectively. Using the Kruskal-Wallis test, residents showed a significant improvement in test scores following the didactic presentation (p = 0.041), while overall results (residents and medical students) also reported a significant difference (p = 0.004). Conclusions: Our results demonstrated that educating family medicine residents and medical students on preoperative evaluation showed significant, quantifiable gains in knowledge following a brief didactic presentation. Given the current gap between guidelines and practice, our results emphasize the need for a formal medical school and residency-based curriculum related to preoperative patient evaluation.

Non-invasive Urine Test for Molecular Classification of Clinical Significance in Newly Diagnosed Prostate Cancer Patients.

Objective: To avoid over-treatment of low-risk prostate cancer patients, it is important to identify clinically significant and insignificant cancer for treatment decision-making. However, no accurate test is currently available. Methods: To address this unmet medical need, we developed a novel gene classifier to distinguish clinically significant and insignificant cancer, which were classified based on the National Comprehensive Cancer Network risk stratification guidelines. A non-invasive urine test was developed using quantitative mRNA expression data of 24 genes in the classifier with an algorithm to stratify the clinical significance of the cancer. Two independent, multicenter, retrospective and prospective studies were conducted to assess the diagnostic performance of the 24-Gene Classifier and the current clinicopathological measures by univariate and multivariate logistic regression and discriminant analysis. In addition, assessments were performed in various Gleason grades/ISUP Grade Groups. Results: The results showed high diagnostic accuracy of the 24-Gene Classifier with an AUC of 0.917 (95% CI 0.892-0.942) in the retrospective cohort (n = 520), AUC of 0.959 (95% CI 0.935-0.983) in the prospective cohort (n = 207), and AUC of 0.930 (95% 0.912-CI 0.947) in the combination cohort (n = 727). Univariate and multivariate analysis showed that the 24-Gene Classifier was more accurate than cancer stage, Gleason score, and PSA, especially in the low/intermediate-grade/ISUP Grade Group 1-3 cancer subgroups. Conclusions: The 24-Gene Classifier urine test is an accurate and non-invasive liquid biopsy method for identifying clinically significant prostate cancer in newly diagnosed cancer patients. It has the potential to improve prostate cancer treatment decisions and active surveillance.

Development and validation of a 25-Gene Panel urine test for prostate cancer diagnosis and potential treatment follow-up.

BACKGROUND: Heterogeneity of prostate cancer (PCa) contributes to inaccurate cancer screening and diagnosis, unnecessary biopsies, and overtreatment. We intended to develop non-invasive urine tests for accurate PCa diagnosis to avoid unnecessary biopsies. METHODS: Using a machine learning program, we identified a 25-Gene Panel classifier for distinguishing PCa and benign prostate. A non-invasive test using pre-biopsy urine samples collected without digital rectal examination (DRE) was used to measure gene expression of the panel using cDNA preamplification followed by real-time qRT-PCR. The 25-Gene Panel urine test was validated in independent multi-center retrospective and prospective studies. The diagnostic performance of the test was assessed against the pathological diagnosis from biopsy by discriminant analysis. Uni- and multivariate logistic regression analysis was performed to assess its diagnostic improvement over PSA and risk factors. In addition, the 25-Gene Panel urine test was used to identify clinically significant PCa. Furthermore, the 25-Gene Panel urine test was assessed in a subset of patients to examine if cancer was detected after prostatectomy. RESULTS: The 25-Gene Panel urine test accurately detected cancer and benign prostate with AUC of 0.946 (95% CI 0.963-0.929) in the retrospective cohort (n = 614), AUC of 0.901 (0.929-0.873) in the prospective cohort (n = 396), and AUC of 0.936 (0.956-0.916) in the large combination cohort (n = 1010). It greatly improved diagnostic accuracy over PSA and risk factors (p < 0.0001). When it was combined with PSA, the AUC increased to 0.961 (0.980-0.942). Importantly, the 25-Gene Panel urine test was able to accurately identify clinically significant and insignificant PCa with AUC of 0.928 (95% CI 0.947-0.909) in the combination cohort (n = 727). In addition, it was able to show the absence of cancer after prostatectomy with high accuracy. CONCLUSIONS: The 25-Gene Panel urine test is the first highly accurate and non-invasive liquid biopsy method without DRE for PCa diagnosis. In clinical practice, it may be used for identifying patients in need of biopsy for cancer diagnosis and patients with clinically significant cancer for immediate treatment, and potentially assisting cancer treatment follow-up.

Dietary Intake, Physical Activity and Metabolic Syndrome in African Americans, Hispanics and Whites.

OBJECTIVE: The objective of the study was to compare the dietary intakes and physical activity levels among Whites, African Americans, and Hispanics with and without metabolic syndrome (MetS). DESIGN: The study was based on secondary analysis of data from the National Health and Nutrition Examination Survey (NHANES) 2011-2012. SETTING: The NHANES's target population is the civilian, noninstitutionalized U.S. SUBJECTS: The sample was made up of 2,449 subjects aged 40 years or more, of both genders, and of three ethnic groups (African Americans, Whites and Hispanics). RESULTS: Mean intakes of food energy, total fat, total saturated fatty acids, total monounsaturated fatty acids, cholesterol, lycopene, selenium and sodium were significantly higher in Whites with MetS. African-Americans with MetS had significantly lower dietary intakes of beta-carotene and total sugars. Also, mean vitamin A and beta-carotene intakes were significantly lower in the Hispanic subjects with MetS. Vigorous and moderate physical activity levels were significantly lower in African Americans and Hispanics with MetS. Computer use was significantly higher in Whites with MetS. CONCLUSIONS: Variables significantly predictive of MetS were age, male gender, African-American ethnicity, BMI, and lycopene intake.

Predictive Factors of Vitamin D Inadequacy among Older Adults in the United States.

Optimal serum vitamin D levels are reported to be associated with many health benefits; however, few studies have determined predictive factors using national level data. An assessment of predictive factors for vitamin D inadequacy was conducted using National Health and Nutrition Examination Survey (NHANES) 2001-2006 data. Using the study sample including adults aged 40 years or more, data analysis was performed using the weighted multivariate logistic regression statistical procedure. The prevalence of vitamin D inadequacy (serum vitamin D <20 ng/ml) was 37.3%. Non-Hispanic Blacks were 6.4 times more likely to demonstrate vitamin D inadequacy compared to non-Hispanic Whites (ORadj=6.351; 95% CI 5.338, 7.555; p<0.0001). Also, female gender was a significant predictor of vitamin D inadequacy (ORadj=1.499; 95% CI 1.315, 1.708; p<0.0001) in multivariate models. Subjects who reported not taking vitamin D supplements in the past 30 days were more than twice as likely to be vitamin D inadequate compared with those who had taken dietary supplements containing vitamin D (ORadj=2.225; 95% CI 1.903, 2.601; p<0.0001). In conclusion, the strongest predictor of vitamin D inadequacy was non-Hispanic Black ethnicity. Other potential predictors included smoking, non-use of vitamin D supplements, abnormal BMI, collecting samples in winter, female gender, perception of own health condition as not excellent, lack of health care, and older age. More focused interventions targeting groups of United States residents with vitamin D inadequacy are needed.

Direct determination of absolute molecular stereochemistry in gas phase by Coulomb explosion imaging.

Bijvoet's method, which makes use of anomalous x-ray diffraction or dispersion, is the standard means of directly determining the absolute (stereochemical) configuration of molecules, but it requires crystalline samples and often proves challenging in structures exclusively comprising light atoms. Herein, we demonstrate a mass spectrometry approach that directly images the absolute configuration of individual molecules in the gas phase by cold target recoil ion momentum spectroscopy after laser ionization-induced Coulomb explosion. This technique is applied to the prototypical chiral molecule bromochlorofluoromethane and the isotopically chiral methane derivative bromodichloromethane.

An integrated randomized intervention to reduce behavioral and psychosocial risks: pregnancy and neonatal outcomes.

While biomedical risks contribute to poor pregnancy and neonatal outcomes in African American (AA) populations, behavioral and psychosocial risks (BPSR) may also play a part. Among low income AA women with psychosocial risks, this report addresses the impacts on pregnancy and neonatal outcomes of an integrated education and counseling intervention to reduce BPSR, as well as the contributions of other psychosocial and biomedical risks. Subjects were low income AA women ≥18 years living in the Washington, DC, metropolitan area and seeking prenatal care. Subjects (n = 1,044) were screened for active smoking, environmental tobacco smoke exposure (ETSE), depression, or intimate partner violence (IPV) and then randomized to intervention (IG) or usual care (UCG) groups. Data were collected prenatally, at delivery, and postpartum by maternal report and medical record abstraction. Multiple imputation methodology was used to estimate missing variables. Rates of pregnancy outcomes (miscarriage, live birth, perinatal death), preterm labor, Caesarean section, sexually transmitted infection (STI) during pregnancy, preterm birth (<37 weeks), low birth weight (<2,500 g), very low birth weight (<1,500 g), small for gestational age, neonatal intensive care unit (NICU) admission, and >2 days of hospitalization were compared between IG and UCG. Logistic regression models were created to predict outcomes based on biomedical risk factors and the four psychosocial risks (smoking, ETSE, depression, and IPV) targeted by the intervention. Rates of adverse pregnancy and neonatal outcomes were high and did not differ significantly between IG and UCG. In adjusted analysis, STI during the current pregnancy was associated with IPV (OR = 1.41, 95% CI 1.04-1.91). Outcomes such as preterm labor, caesarian section in pregnancy and preterm birth, low birth weight, small for gestational age, NICU admissions and >2 day hospitalization of the infants were associated with biomedical risk factors including preexisting hypertension and diabetes, previous preterm birth (PTB), and late initiation of prenatal care, but they were not significantly associated with active smoking, ETSE, depression, or IPV. Neither the intervention to reduce BPSR nor the psychosocial factors significantly contributed to the pregnancy and neonatal outcomes. This study confirms that biomedical factors significantly contribute to adverse outcomes in low income AA women. Biomedical factors outweighed psychosocial factors in contributing to adverse pregnancy and neonatal outcomes in this high-risk population. Early identification and management of hypertension, diabetes and previous PTB in low income AA women may reduce health disparities in birth outcomes. Level of evidence I.

Iron, folate, and vitamin B12 status in the elderly by gender and ethnicity.

OBJECTIVE: National Health and Nutrition Examination Survey 2001-2002 data were used to examine gender and ethnicity relationships to iron, folate, and vitamin B12 status, and anemia in 1770 elderly persons. METHODS: Dependent variables included dietary intakes and biochemical measures of iron, folate, and vitamin B12 status, and hemoglobin. T Tests were performed using SUDAAN software (version 9.0; Research Triangle Institute International, Research Triangle Park, North Carolina). The relationships of gender and ethnicity to adequacy of iron, folate, and vitamin B12 status, and anemia were investigated using chi2 tests. RESULTS: Males had significantly higher nutrient intakes and better biochemical measures of iron status but lower biochemical measures of folate and vitamin B12. Whites were significantly more likely to have nutrient intakes higher than those recommended by the Food and Nutrition Board. No clear pattern of biochemical measures of iron status was seen among the ethnic groups, and there was no significant relationship between iron status and ethnicity. Biochemical measures of folate status were significantly higher in whites and Mexican Americans than in blacks. No significant relationships were found between folate status and ethnicity. Mean serum vitamin B12 was significantly higher in blacks than in whites and was lowest in other Hispanics who were significantly more likely to be vitamin B12 deficient. Blacks had significantly lower mean hemoglobin values than whites and were significantly more likely to be anemic. CONCLUSIONS: Based on biochemical measures, elderly males are at higher risk of folate and vitamin B12 deficiencies. Ethnicity was not significantly related to either iron or folate status. Other Hispanics were significantly more likely to be vitamin B12 deficient.

Reducing psychosocial and behavioral pregnancy risk factors: results of a randomized clinical trial among high-risk pregnant african american women.

OBJECTIVES: We evaluated the efficacy of a primary care intervention targeting pregnant African American women and focusing on psychosocial and behavioral risk factors for poor reproductive outcomes (cigarette smoking, secondhand smoke exposure, depression, and intimate partner violence). METHODS: Pregnant African American women (N = 1044) were randomized to an intervention or usual care group. Clinic-based, individually tailored counseling sessions were adapted from evidence-based interventions. Follow-up data were obtained for 850 women. Multiple imputation methodology was used to estimate missing data. Outcome measures were number of risks at baseline, first follow-up, and second follow-up and within-person changes in risk from baseline to the second follow-up. RESULTS: Number of risks did not differ between the intervention and usual care groups at baseline, the second trimester, or the third trimester. Women in the intervention group more frequently resolved some or all of their risks than did women in the usual care group (odds ratio = 1.61; 95% confidence interval = 1.08, 2.39; P = .021). CONCLUSIONS: In comparison with usual care, a clinic-based behavioral intervention significantly reduced psychosocial and behavioral pregnancy risk factors among high-risk African American women receiving prenatal care.

An intervention to improve postpartum outcomes in African-American mothers: a randomized controlled trial.

OBJECTIVE: To evaluate the efficacy of an integrated multiple risk intervention, delivered mainly during pregnancy, in reducing such risks (cigarette smoking, environmental tobacco smoke exposure, depression, and intimate partner violence) postpartum. METHODS: Data from this randomized controlled trial were collected prenatally and on average 10 weeks postpartum in six prenatal care sites in the District of Columbia. African Americans were screened, recruited, and randomly assigned to the behavioral intervention or usual care. Clinic-based, individually tailored counseling was delivered to intervention women. The outcome measures were number of risks reported postpartum and reduction of these risks between baseline and postpartum. RESULTS: The intervention was effective in significantly reducing the number of risks reported in the postpartum period. In bivariate analyses, the intervention group was more successful in resolving all risks (47% compared with 35%, P=.007, number needed to treat=9, 95% confidence interval [CI] 5-31) and in resolving some risks (63% compared with 54%, P=.009, number needed to treat=11, 95% CI 7-43) as compared with the usual care group. In logistic regression analyses, women in the intervention group were more likely to resolve all risks (odds ratio 1.86, 95% CI 1.25-2.75, number needed to treat=7, 95% CI 4-19) and resolve at least one risk (odds ratio 1.60, 95% CI 1.15-2.22, number needed to treat=9, 95% CI 6-29). CONCLUSION: An integrated multiple risk factor intervention addressing psychosocial and behavioral risks delivered mainly during pregnancy can have beneficial effects in risk reduction postpartum.

Behavioral intervention, exercise, and nutrition education to improve health and fitness (BENEfit) in adolescents with mobility impairment due to spinal cord dysfunction.

BACKGROUND/OBJECTIVE: Determine the effects of a nutrition education and exercise intervention on the health and fitness of adolescents with mobility impairment due to spinal cord dysfunction from myelomeningocele and spinal cord injury. Subjects participated in a 16-week intervention consisting of a behavioral approach to lifestyle change, exercise, and nutrition education to improve fitness (BENEfit) program. Participants were given a schedule of aerobic and strengthening exercises and attended nutrition education and behavior modification sessions every other week along with their parent(s). SUBJECTS: Twenty adolescents (aged 11-18 years, mean 15.4 +/- 2.2 years) with spinal cord dysfunction. METHODS: Subjects were tested immediately prior to starting and upon completion of the program. Aerobic fitness was measured using a ramp protocol with an arm ergometer. Heart rate and oxygen uptake were measured. Values at anaerobic threshold and maximum oxygen uptake were recorded. Peak isokinetic arm and shoulder strength were determined with a dynamometer. Body composition was estimated with dual-energy x-ray absorptiometry. Serum chemistry included measures of cholesterol, high-density lipoprotein, low-density lipoprotein, and triglycerides. RESULTS: Fourteen individuals completed all testing sessions. There was no significant overall change in weight, body mass index, body mass index z-scores, or serum chemistry. Overall, there was a significant increase in whole body lean tissue without a concomitant increase in whole body fat. Fitness measures revealed a significant increase in maximum power output, work efficiency as measured by the amount of power output produced aerobically, and resting oxygen uptake. Strength measurements revealed a significant increase in shoulder extension strength and a trend towards increased shoulder flexion strength. There were no significant changes in high-density lipoprotein, low-density lipoprotein, total cholesterol, or triglycerides. CONCLUSIONS: The BENEfit program shows promise as a method for improving the health and fitness of adolescents with mobility impairments who are at high risk for obesity and obesity-related health conditions.

Recruitment and retention of low-income minority women in a behavioral intervention to reduce smoking, depression, and intimate partner violence during pregnancy.

BACKGROUND: Researchers have frequently encountered difficulties in the recruitment and retention of minorities resulting in their under-representation in clinical trials. This report describes the successful strategies of recruitment and retention of African Americans and Latinos in a randomized clinical trial to reduce smoking, depression and intimate partner violence during pregnancy. Socio-demographic characteristics and risk profiles of retained vs. non-retained women and lost to follow-up vs. dropped-out women are presented. In addition, subgroups of pregnant women who are less (more) likely to be retained are identified. METHODS: Pregnant African American women and Latinas who were Washington, DC residents, aged 18 years or more, and of 28 weeks gestational age or less were recruited at six prenatal care clinics. Potentially eligible women were screened for socio-demographic eligibility and the presence of the selected behavioral and psychological risks using an Audio Computer-Assisted Self-Interview. Eligible women who consented to participate completed a baseline telephone evaluation after which they were enrolled in the study and randomly assigned to either the intervention or the usual care group. RESULTS: Of the 1,398 eligible women, 1,191 (85%) agreed to participate in the study. Of the 1,191 women agreeing to participate, 1,070 completed the baseline evaluation and were enrolled in the study and randomized, for a recruitment rate of 90%. Of those enrolled, 1,044 were African American women. A total of 849 women completed the study, for a retention rate of 79%. Five percent dropped out and 12% were lost-to-follow up. Women retained in the study and those not retained were not statistically different with regard to socio-demographic characteristics and the targeted risks. Retention strategies included financial and other incentives, regular updates of contact information which was tracked and monitored by a computerized data management system available to all project staff, and attention to cultural competence with implementation of study procedures by appropriately selected, trained, and supervised staff. Single, less educated, alcohol and drug users, non-working, and non-WIC women represent minority women with expected low retention rates. CONCLUSION: We conclude that with targeted recruitment and retention strategies, minority women will participate at high rates in behavioral clinical trials. We also found that women who drop out are different from women who are lost to follow-up, and require different strategies to optimize their completion of the study.