Variations in Age-Adjusted Prostate Cancer Incidence Rates by Race and Ethnicity After Changes in Prostate-Specific Antigen Screening Recommendation.

Importance: After publication of US Preventive Task Force Prostate-Specific Antigen (PSA) screening guidelines in 2008 and 2012, there have been documented associations with incidence and stage distributions of prostate cancer. It is unclear if these changes were temporary or differed by age or race and ethnicity. Objective: To assess the association of 2008 and 2012 PSA guidelines with prostate cancer incidence by age and race and ethnicity in the US. Design, Setting, and Participants: This cross-sectional study evaluated prostate cancer incidence from 2005 to 2018 in the US using data from the US Cancer Statistics public use database. Data were analyzed from August 2020 through June 2022. Main Outcomes and Measures: The primary outcome was the year when rates of prostate cancer incidence changed directionality by age and race and ethnicity. Age-adjusted incidence rates of prostate cancer and corresponding 95% CIs were created, followed by join point regression analysis to evaluate trends of age-adjusted incidence rates of prostate cancer by age, race, Hispanic ethnicity, and stage of diagnosis. Results: Among 2 944 387 men with prostate cancer, 2 869 943 (97.5%) men were aged 50 years and older. Men aged 50 years and older accounted for 185 476 of 191 533 Hispanic individuals (96.8%) and 2 684 467 of 2 752 854 non-Hispanic individuals (97.5%). Men aged 50 years and older accounted for 427 016 of 447 847 African American individuals (95.4%), 12 141 of 12 470 American Indian or Alaska Native individuals (97.4%), 61 126 of 62 159 Asian or Pacific Islander individuals (98.3%), and 2 294 171 of 2 344 392 White individuals (97.9%). Men with unknown race (77 519 men) were excluded from the analysis. A decrease in age-adjusted rate of prostate cancer after the 2008 guideline change was observed in all age groups by race and ethnicity. For example, among African American men ages 65 to 74 years, 10 784 of 807 080 men (1.34%) had a prostate cancer diagnosis in 2007 vs 10 714 of 835 548 men in 2008 (1.28%). The mean annual age-adjusted incidence rates of prostate cancer per 100 000 men were 157.7 men (95% CI, 157.4-158.0 men) in 2005 to 2008 and 131.9 men (95% CI, 131.6-132.2 men) in 2009 to 2012. The number of inflections and annual percent changes (APCs) for segments separated by inflections varied by age, race, and Hispanic ethnicity. For men ages 65 to 74 years, the APC was -6.53 (95% CI, -9.28 to -3.69) for 2009 to 2014 among African American men (2 join points), -5.96 (95% CI, -6.84 to -5.07) for 2007 to 2018 among American Indian or Alaska Native men (1 join point), -6.52 (95% CI, -9.22 to -3.74) for 2007 to 2014 among Asian or Pacific Islander men (2 join points), -7.92 (95% CI, -11.36 to -4.35) for 2009 to 2014 among Hispanic men (2 join points), and -7.02 (95% CI, -9.41 to -4.57) for 2007 to 2014 among White men (2 join points).‬‬‬‬‬‬‬‬. Conclusions and Relevance: In this study, men in different age, race, and ethnicity groups had different APC patterns after 2008 and 2012 PSA screening guideline changes. These findings may provide important data on the timing and durations of changes in cancer diagnoses that are associated with changes in PSA screening recommendations and may be valuable for targeted strategies to reduce regional- and distant-staged cancers.

The need to study rural cancer outcome disparities at the local level: a retrospective cohort study in Kansas and Missouri.

BACKGROUND: Rural residence is commonly thought to be a risk factor for poor cancer outcomes. However, a number of studies have reported seemingly conflicting information regarding cancer outcome disparities with respect to rural residence, with some suggesting that the disparity is not present and others providing inconsistent evidence that either urban or rural residence is associated with poorer outcomes. We suggest a simple explanation for these seeming contradictions: namely that rural cancer outcome disparities are related to factors that occur differentially at a local level, such as environmental exposures, lack of access to care or screening, and socioeconomic factors, which differ by type of cancer. METHODS: We conducted a retrospective cohort study examining ten cancers treated at the University of Kansas Medical Center from 2011 to 2018, with individuals from either rural or urban residences. We defined urban residences as those in a county with a U.S. Department of Agriculture Urban Influence Code (UIC) of 1 or 2, with all other residences defines a rural. Inverse probability of treatment weighting was used to create a pseudo-sample balanced for covariates deemed likely to affect the outcomes modeled with cumulative link and weighted Cox-proportional hazards models. RESULTS: We found that rural residence is not a simple risk factor but rather appears to play a complex role in cancer outcome disparities. Specifically, rural residence is associated with higher stage at diagnosis and increased survival hazards for colon cancer but decreased risk for lung cancer compared to urban residence. CONCLUSION: Many cancers are affected by unique social and environmental factors that may vary between rural and urban residents, such as access to care, diet, and lifestyle. Our results show that rurality can increase or decrease risk, depending on cancer site, which suggests the need to consider the factors connected to rurality that influence this complex pattern. Thus, we argue that such disparities must be studied at the local level to identify and design appropriate interventions to improve cancer outcomes.

A Midwest Tri-State Study of Overall Survival in Ovarian Cancer with Adjuvant Chemotherapy.

BACKGROUND: Overall survival associated with National Comprehensive Cancer Network (NCCN) adjuvant chemotherapy treatment guideline using population-based surveillance data is limited. This study examined overall survival and compliance to the NCCN guideline for adjuvant chemotherapy. METHODS: The Midwest Ovarian Cancer Study was a collaborative project between 3 state cancer registries (Iowa, Kansas, and Missouri), Westat, and the Centers for Disease Control and Prevention. A standardized protocol was used to ascertain International Federation of Gynecology and Obstetrics (FIGO) stage-specific adjuvant chemotherapy. Primary epithelial ovarian cancers with FIGO stages IA/IB grade 3, IC, and II-IV with histologies 8000-8576 and 8930-9110 were included in this study. The Kaplan-Meier method was used to calculate survival functions. Adjusted hazard ratio (HR) was analyzed for all-cause mortality associated with NCCN compliance with adjuvant chemotherapy after adjusting for stage at diagnosis and comorbidity. RESULTS: Sixtynine percent (523 of 756 eligible) were compliant with NCCN guidelines. Compliance was significantly different by age at diagnosis and insurance type (both P < .0001). The overall survival was significantly different by age group, census tract median income, histologic subtype, and tumor grade (all P < .0001). The adjusted HR of noncompliance with adjuvant chemotherapy guideline was 3.2 (95% CI, 2.600-3.911). CONCLUSIONS: Better overall survival in patients who had received NCCN-recommended adjuvant chemotherapy was confirmed. IMPACT: The survival benefit was 7% higher over 4 years after diagnosis when considering FIGO stage-specific chemotherapy and the corresponding number of cycles. Using the chemotherapy data field that is collected by statewide cancer registries underestimated the overall survival.

Improving the efficiency of clinical trials by standardizing processes for Investigator Initiated Trials.

Early phase clinical trials are the first step in testing new medications and therapeutics developed by clinical and biomedical investigators. These trials aim to find a safe dose of a newly targeted drug (phase I) or find out more about the side effects and early signals of treatment efficacy (phase II). In a research institute, many biomedical investigators in oncology are encouraged to initiate such trials early in their careers as part of developing their research portfolio. These investigator-initiated trials (IITs) are funded internally by the University of Kansas Cancer Center or partially funded by pharmaceutical companies. As financial, administrative, and practical considerations play an essential role in the successful completion of IITs, it is imperative to efficiently allocate resources to plan, design, and execute these studies within the allotted time. This manuscript describes monitoring tools and processes to improve the efficiency, cost-effectivness, and reliability of IITs. The contributions of this team to processes such as: participant recruitment, feasibility analysis, clinical trial design, accrual monitoring, data management, interim analysis support, and final analysis and reporting are described in detail. This manuscript elucidates how, through the aid of technology and dedicated personnel support, the efficiency of IIT-related processes can be improved. Early results of these initiatives look promising, and the Biostatistics and Informatics team intends to continue fostering innovative methodologies to enhance cancer research by improving the efficiency of IITs.

Impact of Adding Telephone-Based Care Coordination to Standard Telephone-Based Smoking Cessation Counseling Post-hospital Discharge: a Randomized Controlled Trial.

BACKGROUND: Cessation counseling and pharmacotherapy are recommended for hospitalized smokers, but better coordination between cessation counselors and providers might improve utilization of pharmacotherapy and enhance smoking cessation. OBJECTIVE: To compare smoking cessation counseling combined with care coordination post-hospitalization to counseling alone on uptake of pharmacotherapy and smoking cessation. DESIGN: Unblinded, randomized clinical trial PARTICIPANTS: Hospitalized smokers referred from primarily rural hospitals INTERVENTIONS: Counseling only (C) consisted of telephone counseling provided during the hospitalization and post-discharge. Counseling with care coordination (CCC) provided similar counseling supplemented by feedback to the smoker's health care team and help for the smoker in obtaining pharmacotherapy. At 6 months post-hospitalization, persistent smokers were re-engaged with either CCC or C. MAIN MEASURES: Utilization of pharmacotherapy and smoking cessation at 3, 6, and 12 months post-discharge. KEY RESULTS: Among 606 smokers randomized, 429 (70.8%) completed the 12-month assessment and 580 (95.7%) were included in the primary analysis. Use of any cessation pharmacotherapy between 0 and 6 months (55.2%) and between 6 and 12 months (47.1%) post-discharge was similar across treatment arms though use of prescription-only pharmacotherapy between months 6-12 was significantly higher in the CCC group (30.1%) compared with the C group (18.6%) (RR, 1.61 (95% CI, 1.08, 2.41)). Self-reported abstinence rates of 26.2%, 20.3%, and 23.4% at months 3, 6, and 12, respectively, were comparable across the two treatment arms. Of those smoking at month 6, 12.5% reported abstinence at month 12. Validated smoking cessation at 12 months was 19.3% versus 16.9% in the CCC and C groups, respectively (RR, 1.13 (95% CI, 0.80, 1.61)). CONCLUSION: Supplemental care coordination, provided by counselors outside of the health care team, failed to improve smoking cessation beyond that achieved by cessation counseling alone. Re-engagement of smokers 6 months post-discharge can lead to new quitters, at which time care coordination might facilitate use of prescription medications. TRIAL REGISTRATION: NCT01063972.

Subgroup identification of early preterm birth (ePTB): informing a future prospective enrichment clinical trial design.

BACKGROUND: Despite the widely recognized association between the severity of early preterm birth (ePTB) and its related severe diseases, little is known about the potential risk factors of ePTB and the sub-population with high risk of ePTB. Moreover, motivated by a future confirmatory clinical trial to identify whether supplementing pregnant women with docosahexaenoic acid (DHA) has a different effect on the risk subgroup population or not in terms of ePTB prevalence, this study aims to identify potential risk subgroups and risk factors for ePTB, defined as babies born less than 34 weeks of gestation. METHODS: The analysis data (N = 3,994,872) were obtained from CDC and NCHS' 2014 Natality public data file. The sample was split into independent training and validation cohorts for model generation and model assessment, respectively. Logistic regression and CART models were used to examine potential ePTB risk predictors and their interactions, including mothers' age, nativity, race, Hispanic origin, marital status, education, pre-pregnancy smoking status, pre-pregnancy BMI, pre-pregnancy diabetes status, pre-pregnancy hypertension status, previous preterm birth status, infertility treatment usage status, fertility enhancing drug usage status, and delivery payment source. RESULTS: Both logistic regression models with either 14 or 10 ePTB risk factors produced the same C-index (0.646) based on the training cohort. The C-index of the logistic regression model based on 10 predictors was 0.645 for the validation cohort. Both C-indexes indicated a good discrimination and acceptable model fit. The CART model identified preterm birth history and race as the most important risk factors, and revealed that the subgroup with a preterm birth history and a race designation as Black had the highest risk for ePTB. The c-index and misclassification rate were 0.579 and 0.034 for the training cohort, and 0.578 and 0.034 for the validation cohort, respectively. CONCLUSIONS: This study revealed 14 maternal characteristic variables that reliably identified risk for ePTB through either logistic regression model and/or a CART model. Moreover, both models efficiently identify risk subgroups for further enrichment clinical trial design.

Impact of Telephone-Based Care Coordination on Use of Cessation Medications Posthospital Discharge: A Randomized Controlled Trial.

INTRODUCTION: Smokers benefit from ongoing cessation support upon leaving the hospital and returning to their home environment. This study examined the impact of telephone-delivered care coordination on utilization of and adherence to cessation pharmacotherapy after hospital discharge. METHODS: Inpatient smokers (n = 606) were randomized to receive counseling with care coordination (CCC) or counseling alone (C) for smoking cessation. Both groups received written materials and telephone-based cessation counseling during hospitalization and postdischarge. CCC recipients received help in selecting, obtaining, and refilling affordable pharmacotherapy prescriptions during and after hospitalization. Study outcomes included self-reported utilization, duration of use, and type of medication during the 3 months postdischarge. RESULTS: Of the 487 (80%) of participants completing 3-month follow-up, 211 (43.3%) reported using cessation pharmacotherapy postdischarge; this did not differ by study arm (CCC: 44.7%, C: 42.0%, p = .55). Use of pharmacotherapy postdischarge was associated with smoking at least 20 cigarettes/day at baseline (odds ratio [OR]: 1.48; 95% confidence interval [CI]: 1.00-2.19) and receipt of pharmacotherapy during hospitalization (OR: 4.00; 95% CI: 2.39-6.89). Smokers with Medicaid (OR: 2.29; 95% CI: 1.32-4.02) or other insurance (OR: 1.69; 95% CI: 1.01-2.86) were more likely to use pharmacotherapy postdischarge than those with no health care coverage. Less than one in four (23.8% of CCC; 22.2% of C) continued pharmacotherapy beyond 4 weeks. CONCLUSIONS: Supplemental care coordination did not improve use of postdischarge pharmacotherapy beyond that of inpatient treatment and behavioral counseling. Insurance coverage and use of medications during the hospitalization are associated with higher use of evidence-based treatment postdischarge. IMPLICATIONS: Many hospitalized smokers do not receive the benefits of cessation pharmacotherapy postdischarge and telephone quitline programs often fail to help smokers procure pharmacotherapy. Thus, effective strategies are needed to improve utilization and adherence to evidence-based cessation therapies when smokers leave the hospital. We found that use of postdischarge pharmacotherapy was strongly associated with receipt of pharmacotherapy during the hospitalization and with the availability of insurance to cover the costs of treatment. Additional efforts to coordinate pharmacotherapy services did not improve either utilization or adherence to therapy.

Changes in Postural Control After a Ball-Kicking Balance Exercise in Individuals With Chronic Ankle Instability.

CONTEXT: Rehabilitation programs for patients with chronic ankle instability (CAI) generally involve balance-perturbation training (BPT). Anticipatory postural adjustments (APAs) and compensatory postural adjustments (CPAs) are the primary strategies used to maintain equilibrium during body perturbations. Little is known, however, about how APAs and CPAs are modified to promote better postural control for individuals with CAI after BPT. OBJECTIVE: To investigate the effect of BPT that involves kicking a ball on postural-control strategies in individuals with CAI. DESIGN: Randomized controlled clinical trial. SETTING: Laboratory. PATIENTS OR OTHER PARTICIPANTS: We randomly assigned 44 volunteers with CAI to either a training group (TG; 11 women, 11 men; age = 24 ± 4 years, height = 173.0 ± 9.8 cm, mass = 72.64 ± 11.98 kg) or control group (CG; 11 women, 11 men; age = 22 ± 3 years, height = 171.0 ± 9.7 cm, mass = 70.00 ± 11.03 kg). INTERVENTION(S): The TG performed a single 30-minute training session that involved kicking a ball while standing on 1 foot. The CG received no intervention. MAIN OUTCOME MEASURE(S): The primary outcome was the sum of the integrated electromyographic activity (∑∫EMG) of the lower extremity muscles in the supporting limb that were calculated during typical intervals for APAs and CPAs. A secondary outcome was center-of-pressure displacement during similar intervals. RESULTS: In the TG after training, the ∑∫EMG decreased in both dorsal and ventral muscles during compensatory adjustment (ie, the time interval that followed lower limb movement). During this interval, muscle activity (∑∫EMG) was less in the TG than in the CG. Consequently, center-of-pressure displacement increased during the task after training. CONCLUSIONS: A single session of ball-kicking BPT promoted changes in postural-control strategies in individuals with CAI. These results should stimulate new and more comprehensive studies to investigate the effect of this and other BPT techniques on postural control in patients with CAI.

Role of outpatient physicians in reporting of hematopoietic malignancies for statewide surveillance.

BACKGROUND: The role of physicians in outpatient setting in reporting of hematopoietic malignancies is not well known. OBJECTIVES: This study described the approaches that Kansas Cancer Registry (KCR) used to ascertain completeness of hematopoietic malignancies reporting at the state level. Our study also examined the role of hematologists, oncologists and primary care physicians (PCP) in outpatient setting in reporting of hematopoietic malignancies. METHODS: KCR engaged all outpatient hematologists, oncologists, and a sample of PCPs who cared for patients in geographic areas where there was limited access to hematologists/oncologists. Cases that met reportable eligibility were identified using the ICD- 9-CM codes from the medical record disease index files and confirmed by reviewing patient medical records. Confirmed cases were then abstracted and sent to the registry. The study focused on 2010 diagnosed Kansan cases. RESULTS: Of the total 2010 diagnosed cases, 18.7 percent were reported solely by outpatient physicians (17.0 percent reported by outpatient hematologists/ oncologists and 1.7 percent reported by outpatient PCPs only). Fifty-eight percent of polycythemia vera was diagnosed and treated by outpatient hematologists, oncologists, and some PCPs. Using reportable ICD-9-CM codes only for hematopoietic malignancies causes an overestimation of the true reportable hematopoietic malignancies cases. CONCLUSION: Outpatient physicians are critical in the scheme of care for hematologic malignancies. Therefore collection of cancer data from these outpatient providers by a well operated statewide registry provides a far more accurate picture of what is really going on with hematopoietic malignancies.

Impact of patient-level risk adjustment on the findings about nurse staffing and 30-day mortality in veterans affairs acute care hospitals.

BACKGROUND: Studies about nurse staffing and patient outcomes often lack adequate risk adjustment because of limited access to patient information. OBJECTIVE: The aim of this study was to examine the impact of patient-level risk adjustment on the associations of unit-level nurse staffing and 30-day inpatient mortality. METHODS: This retrospective cross-sectional study included 284,097 patients discharged during 2007-2008 from 446 acute care nursing units at 128 Veterans Affairs medical centers. The association of nurse staffing with 30-day mortality was assessed using hierarchical logistic models under three levels of risk-adjustment conditions: using no patient information (low), using patient demographics and diagnoses (moderate), or using patient demographics and diagnoses plus physiological measures (high). RESULTS: Discriminability of the models improved as the level of risk adjustment increased. The c-statistics for models of low, moderate, and high risk adjustment were 0.64, 0.74, and 0.88 for non-ICU patients and 0.66, 0.76, and 0.88 for ICU patients. For non-ICU patients, higher RN skill mix was associated with lower 30-day mortality across all three levels of risk adjustment. For ICU patients, higher total nursing hours per patient day was strongly associated with higher mortality with moderate risk adjustment (p = .0002), but this counterintuitive association was not significant with low or high risk adjustment. DISCUSSION: Inadequate risk adjustment may lead to biased estimates about nurse staffing and patient outcomes. Combining physiological measures with commonly used administrative data is a promising risk-adjustment approach to reduce potential biases.

Short-term soy isoflavone intervention in patients with localized prostate cancer: a randomized, double-blind, placebo-controlled trial.

PURPOSE: We describe the effects of soy isoflavone consumption on prostate specific antigen (PSA), hormone levels, total cholesterol, and apoptosis in men with localized prostate cancer. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a double-blinded, randomized, placebo-controlled trial to examine the effect of soy isoflavone capsules (80 mg/d of total isoflavones, 51 mg/d aglucon units) on serum and tissue biomarkers in patients with localized prostate cancer. Eighty-six men were randomized to treatment with isoflavones (n=42) or placebo (n=44) for up to six weeks prior to scheduled prostatectomy. We performed microarray analysis using a targeted cell cycle regulation and apoptosis gene chip (GEArrayTM). Changes in serum total testosterone, free testosterone, total estrogen, estradiol, PSA, and total cholesterol were analyzed at baseline, mid-point, and at the time of radical prostatectomy. In this preliminary analysis, 12 genes involved in cell cycle control and 9 genes involved in apoptosis were down-regulated in the treatment tumor tissues versus the placebo control. Changes in serum total testosterone, free testosterone, total estrogen, estradiol, PSA, and total cholesterol in the isoflavone-treated group compared to men receiving placebo were not statistically significant. CONCLUSIONS/SIGNIFICANCE: These data suggest that short-term intake of soy isoflavones did not affect serum hormone levels, total cholesterol, or PSA. TRIAL REGISTRATION: ClinicalTrials.gov NCT00255125.

Identifying incident oral and pharyngeal cancer cases using Medicare claims.

BACKGROUND: Baseline and trend data for oral and pharyngeal cancer incidence is limited. A new algorithm was derived using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database to create an algorithm to identify incident cases of oral and pharyngeal cancer using Medicare claims. METHODS: Using a split-sample approach, Medicare claims' procedure and diagnosis codes were used to generate a new algorithm to identify oral and pharyngeal cancer cases and validate its operating characteristics. RESULTS: The algorithm had high sensitivity (95%) and specificity (97%), which varied little by age group, sex, and race and ethnicity. CONCLUSION: Examples of the utility of this algorithm and its operating characteristics include using it to derive baseline and trend estimates of oral and pharyngeal cancer incidence. Such measures could be used to provide incidence estimates where they are lacking or to serve as comparator estimates for tumor registries.

Clinicopathologic correlation of vitamin D receptor expression with retinoid X receptor and MIB-1 expression in primary and metastatic osteosarcoma.

Vitamin D, in addition to its effects on bone, is important in cell cycle regulation. Vitamin D receptor (VDR) has been identified in breast, prostate, and colon cancers, as well as in canine and human osteosarcoma (OS) cell lines; however, it has not been well investigated in human OS-archived specimens. We correlated VDR, retinoid X receptor (RXR), and MIB-1 (Ki-67) expression in 110 archived OS cases with several clinicopathologic parameters including patient's age, sex, tumor location, tumor grade, and type and metastatic status. The expression of VDR and RXR was identified in human OS tissue obtained from primary and metastatic OS archival tissue. No statistically significant difference was found in VDR expression in relation with tumor grade, type, age, sex, or location. The expression of RXR was highest in higher-grade (P = .0006) and metastatic tumors but remained unchanged when correlated with tumor type, age, sex, or location. The expression of MIB-1 was statistically elevated in higher-grade tumors (P = .001), patients 25 years or younger (P = .04), tumors located in extremities (P = .005), and metastatic lesions, but was not impacted by tumor type or patient's sex. Proliferative activity was significantly reduced after treatment, as the mean MIB-1 expression dropped from 11% in primary biopsy samples to 6% in resection specimens. There appears to be a relationship between proliferative tumor activity and tumor grade, location, and metastasis. Additional studies on the analysis of the effects of vitamin D and RXR on OS proliferation, apoptosis, and differentiation are critical to further evaluate their potential role in OS treatment.

Effect of 25-hydroxyvitamin D3 and 1 α,25 dihydroxyvitamin D3 on differentiation and apoptosis of human osteosarcoma cell lines.

Osteosarcoma (OS) is a malignant bone tumor predominantly affecting children and adolescents. OS has a 60% survival rate with current treatments; hence, there is a need to identify novel adjuncts to chemotherapeutic regimens. In this pilot study, we investigated the dose-response to 1α,25-dihdroxyvitamin D(3) (1,α 25(OH)(2) D(3)) and 25-hydroxyvitamin D(3) (25(OH)D(3)) by human OS cell lines, SaOS-2, and 143B. We hypothesized that 1,α 25(OH)(2) D(3) and 25(OH)D(3) would stimulate differentiation and induce apoptosis in OS cells in a dose-dependent manner. Human OS cell lines, SaOS-2, and 143B, were treated with 1,α 25(OH)(2)D(3) or 25(OH)D(3) or an ethanol control, respectively, at concentrations ranging from 1 to 1,000 nM. Ki67 (a marker of cellular proliferation) immunocytochemistry revealed no significant changes in the expression of Ki-67 or MIB-1 in 1α,25(OH)(2)D(3) or 25(OH)D(3) treated SaOS-2 or 143B cells. Both control and 1α,25(OH)(2) D(3) treated SaOS-2 and 143B cells expressed vitamin D receptor (VDR). Markers of osteoblastic differentiation in 143B cells and SaOS-2 cells were induced by both 25(OH)D(3) and 1α,25(OH)(2) D, and evident by increases in alkaline phosphatase (ALP) activity, osteocalcin (OCN) mRNA expression, and mineralization of extra-cellular matrix (ECM) by alizarin red staining. An increasing trend in apoptosis in response to 25(OH)D(3), in both SaOS-2 and 143B cells was detected by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) staining. With 1α,25(OH)(2)D(3) treatment, apoptosis was evident at higher concentrations only. These preliminary findings suggest that OS cells express VDR and respond to 25(OH)D(3) and 1α,25(OH)(2)D(3) by undergoing differentiation and apoptosis.

Effect of the staging schema on melanoma cancer reporting, 1999 to 2006.

BACKGROUND: Staging schemas have changed multiple times over the past 10 years. OBJECTIVE: We sought to examine the impact of staging schemas on the distribution of stages at diagnosis over time. METHODS: We examined the stage at diagnosis for melanoma cancer cases diagnosed between 1999 and 2006 using data provided by the Surveillance, Epidemiology, and End Results (SEER) and National Program of Cancer Registries (NPCR) programs. The staging schemas were summary staging 1977 (SS1977), summary staging 2000 (SS2000), derived SS2000, and SEER historic staging systems. RESULTS: Melanoma was predominantly staged as a localized disease in all schemas. Using SEER data, the proportion of localized melanomas diagnosed in 2001 to 2003 using SS2000 was about 2.5% lower than the proportion diagnosed in 1999 to 2000 using SS1977, whereas the proportion of cases staged as regional was 2.7% higher using the SS2000 than SS1977. The distribution of stages for cases diagnosed in 2001 to 2003 using SS2000 was similar to that for cases diagnosed in 2004 to 2006 using a derived SS2000. Shift in stage distribution among SS1977, SS2000, and SEER historic staging was found to be about 6% (localized to regional) and about 17.5% (unknown to regional stage). The distribution of changes in stage observed for the SEER cases was not evident for cases from NPCR. LIMITATIONS: SEER historic staging was not available for NPCR cases. CONCLUSION: Changes in staging rules resulted in cases being moved from the localized to the regional stage and from unknown to the regional stage. Without staging rules that have been consistently applied to melanomas over many years, surveillance of prevention, treatment, and control of this condition is difficult.

Comparing patient and nurse specialist reports of causative factors of depression related to heart failure.

PURPOSE: The purpose of this study was to compare participants' and a psychiatric nurse specialist's reports on factors precipitating depression and to validate a depression screening instrument. DESIGN AND METHODS: Participants were screened for and asked to self-report causative factors of their depression. Participants with moderately severe and severe depressive symptoms received a psychiatric nurse specialist assessment. FINDINGS: Participants self-reported several causative factors of depression. The psychiatric nurse specialist discovered these plus additional factors. The screening instrument was found to be reliable and valid for the measurement of depressive symptoms. PRACTICE IMPLICATIONS: Participant self-report identifies many causative factors of depression. The psychiatric nurse specialist identifies additional factors, allowing individualized diagnoses and treatments.

High accuracy of narrow band imaging without magnification for the real-time characterization of polyp histology and its comparison with high-definition white light colonoscopy: a prospective study.

OBJECTIVES: Standard white light colonoscopy has limited ability to differentiate between polyp types (adenomatous vs. hyperplastic). Narrow band imaging (NBI) highlights the superficial mucosal/vascular patterns on polyps and may facilitate real-time characterization of polyp histology. The aim of this study was to prospectively evaluate and compare the diagnostic characteristics of high-definition white light colonoscopy (HDWL) and NBI without magnification in the real-time prediction of polyp histology (adenomatous vs. hyperplastic) by evaluating the surface mucosal and vascular patterns. METHODS: We conducted a prospective comparative study in a tertiary referral center. A total of 100 patients referred for screening or surveillance colonoscopy were prospectively enrolled and underwent colonoscopy using a high-definition colonoscope with NBI capability. Every polyp detected was initially evaluated with HDWL followed by NBI for the presence of surface mucosal/vascular patterns. Based on these patterns, polyp histology was predicted by both modalities. The main outcome measurements were: (i) diagnostic characteristics of HDWL and NBI in predicting polyp histology and (ii) impact of polyp size and learning effect (first half of study vs. second half) on the ability of NBI to predict adenomas. RESULTS: A total of 236 polyps were detected in 100 patients-143 adenomas, 77 hyperplastic, and 16 others. Surface patterns (type A: hyperplastic; type B: adenomatous) were recognized in all polyps with NBI (100%) compared to 45% with HDWL. For predicting adenomas, NBI had a significantly higher sensitivity and greater accuracy (96 and 93% respectively) compared with HDWL (38 and 61% respectively) (all P<0.0001). Although the accuracy of NBI for predicting adenomas improved with increasing polyp size (< or =5 mm; 6-9 mm; > or =10 mm) and in the second half compared with the first half of the study, these differences were not statistically significant. CONCLUSIONS: Using a simple surface mucosal/vascular pattern classification, NBI without magnification was highly accurate and significantly superior to HDWL for the real-time prediction of adenomas.

Recognition of surface mucosal and vascular patterns of colon polyps by using narrow-band imaging: interobserver and intraobserver agreement and prediction of polyp histology.

BACKGROUND: The 2 main types of colon polyps are adenomas and hyperplastic. Pit patterns on the surface of polyps have been described by using magnification chromoendoscopy, which can help differentiate between polyp types. Narrow band imaging (NBI) is a novel technology that enhances the visualization of surface mucosal and vascular patterns on the polyp surface. Earlier we described, in a pilot study, patterns seen on the polyp surface with NBI that can help differentiate between adenomas and hyperplastic polyps with a high degree of accuracy. OBJECTIVE: The aim of this study was to evaluate the interobserver and intraobserver agreement (among endoscopists) for the NBI surface mucosal and vascular patterns and prediction of polyp histology and the accuracy of the investigators to predict polyp histology based on these patterns. SETTING: Kansas City Veterans Affairs Medical Center. METHODS: NBI images of the polyp surface mucosal and vascular patterns obtained in our pilot trial were retrieved. A teaching set of 20 images was selected to educate and demonstrate the polyp patterns to 4 endoscopists. Subsequently, the test set of images was evaluated by the 4 endoscopists for quality, polyp pattern, and prediction of polyp type. Interobserver agreement (k value) was calculated among the 4 assessors for the polyp patterns and predicted histology. By using the final histology as the criterion standard, the accuracy of polyp-type prediction was calculated for each assessor. After a period of 2 months, all polyp images were reevaluated by the assessors (as before), and all findings were recorded in a similar fashion. These results were used for calculation of intraobserver agreement (k value) and the accuracy of the assessors in predicting polyp type. RESULTS: Photographs of 65 polyps were included in the test set and were evaluated by the 4 assessors. Thirty-eight polyps were adenomatous, and 27 were hyperplastic. The kappa value for the interobserver agreement for polyp surface pattern was 0.57 (moderate) and for prediction of polyp type was 0.63 (substantial). The kappa value for the intraobserver agreement of the 4 assessors for the surface patterns was 0.70, 0.65, 0.60, and 0.79, and for the prediction of polyp type was 0.87, 0.71, 0.61, 0.81. The accuracy to predict polyp type ranged from 80% to 86% for the 4 assessors in the first reading and from 85% to 91% in the second reading, with every assessor showing an improvement in accuracy in the second reading. LIMITATIONS: A single-center study, with a limited number of polyps. CONCLUSIONS: This initial evaluation showed that the NBI polyp patterns described in our pilot study are reproducible, easy to learn, reasonably accurate, and have the potential for use in daily clinical practice for the real-time differentiation of colon polyps.

Evaluating the Completeness of the SEER-Medicare Linked Database for Oral and Pharyngeal Cancer.

Oral and pharyngeal cancer is a persistent oral health problem. Baseline and trend data to measure progress are lacking. Our long-term goal is to create an algorithm using Medicare claims to identify oral and pharyngeal cancer cases among those ages 65 and older. The goal of this project was to assess the completeness of the SEER-Medicare linked database for identifying incident oral and pharyngeal cancer cases. We compared incidence rates from the "gold-standard" SEER limited-use database to those from the SEER-Medicare linked database using a quasi-likelihood extension of Poisson regression, allowing for over-dispersion. Adjustment for age, sex, race and ethnicity, and interaction terms between these explanatory variables with data source were used to assess the completeness of the SEER-Medicare linked database among these subgroups. Approximately 6.4% of the cases were missing from the SEER-Medicare linked database. The completeness varied by race and ethnicity (p=0.066). Future development of an algorithm to identify oral and pharyngeal cancer cases using Medicare claims alone can potentially identify over 93% of the cases; however, Hispanic, non-Hispanic black, and non-Hispanic other race and ethnicity subgroups will be less likely than non-Hispanic whites to be identified in such future algorithms.

Sex differences in stroke recovery.

INTRODUCTION: This study examined differences between men and women in the ability to perform basic activities of daily living, instrumental activities of daily living, and higher physical functioning after stroke. The objective of the study was to determine whether sex differences in stroke recovery can be explained by depressive status beyond older age, stroke severity, prestroke physical functioning, and other medical comorbidities. METHODS: A total of 459 stroke patients were recruited from acute and subacute facilities in an urban midwestern community. These patients were followed prospectively from stroke onset until 6 months poststroke. All study participants were assessed using standardized stroke outcome measures, including the National Institutes of Health Stroke Scale, the Barthel Activities of Daily Living Index, the Lawton Instrumental Activities of Daily Living scale, and the SF-36 Health Survey physical functioning scale. The Geriatric Depression Scale was used to assess depressive status. Each outcome was measured at baseline (within 2 weeks of stroke onset), as well as 1, 3, and 6 months poststroke. Prestroke physical functioning, stroke characteristics, and comorbidities were also assessed at baseline. RESULTS: Female patients in the study were older than male patients, with a mean age of 71 years for women vs 69 years for men. Female patients reported lower prestroke physical functioning than their male counterparts. Six months after stroke, women in the study were less likely than the men to achieve a score of > or = 95 on the Barthel Activities of Daily Living Index (hazards ratio [HR] = 0.68; 95% confidence interval [CI], 0.52-0.90), carry out eight of nine instrumental activities of daily living without assistance (HR = 0.46; 95% CI, 0.30-0.68), and score > or = 90 on the SF-36 Health Survey physical functioning scale (HR = 0.54; 95% CI, 0.28-1.01). When age, prestroke physical functioning, stroke severity, and depressive status at baseline were controlled in the analysis, women in the study continued to be less likely (HR = 0.51; 95% CI, 0.32-0.79) than men in the study to be able to carry out eight of nine instrumental activities of daily living completely without assistance, but there were no observed sex differences in achievement of independence in basic activities of daily living or higher physical functioning. CONCLUSION: Prestroke physical functioning and depressive symptoms are important factors in the investigation of sex differences in stroke recovery. Lower recovery of activities of daily living and physical functioning in women after stroke may be due to multifactorial effects of older age, poor physical function prior to stroke onset, and depressive status after stroke.