In order to investigate whether short- or long-term glycemic fluctuations could induce oxidative stress and chronic inflammation, we evaluated the relationships between glycemic variability, oxidative stress markers, and high-sensitivity C-reactive protein (hs-CRP). We enrolled 34 patients with type 2 diabetes. As a measure of short-term glycemic variability, mean amplitude of glycemic excursions (MAGE) was computed from continuous glucose monitoring system data. For determining long-term glycemic variability, we calculated the standard deviation (SD) of hemoglobin A1c (HbA1c) levels measured over a 2-year period. Levels of oxidative stress markers: 8-iso-prostaglandin F2α (8-iso-PGF2α), thiobarbituric acid-reactive substance (TBARS), 8-hydroxydeoxyguanosine (8-OHdG), and hs-CRP were measured. MAGE was significantly correlated with the SD of HbA1c levels (r = 0.73, p < 0.001) but not with HbA1c level. The levels of hs-CRP, TBARS, 8-OHdG, and 8-iso-PGF2α were significantly correlated with MAGE (r = 0.54, p = 0.001; r = 0.82, p < 0.001; r = 0.70, p < 0.001; r = 0.60, p < 0.001) and the SD of HbA1c levels (r = 0.53, p = 0.001; r = 0.73, p < 0.001; r = 0.69, p < 0.001; r = 0.43, p = 0.01) but not with HbA1c level. Relationships between 8-iso-PGF2α and MAGE or the SD of HbA1c levels remained significant after adjusting for other markers of diabetic control (R (2) = 0.684, R (2) = 0.595, p < 0.001, respectively). Both acute and chronic blood glucose variability can induce oxidative stress and chronic inflammation.

Background: A fluctuating blood glucose level is one of the risks of chronic complications in diabetes. Previous studies indicated that hemoglobin A1c (HbA1c) values apparently improved after initiation of self-monitoring blood glucose (SMBG). The purpose of this study is to investigate the relationship between the frequency of SMBG, long-term fluctuatation of HbA1c, and risks of chronic complications in diabetes. Methods: We enrolled 1052 patients with type 2 diabetes. The mean follow-up was 4.7 years. The HbA1c level and frequency of SMBG were recorded every 3 months. Non-mydriatic retinal photography, semiquantitative neuropathy assessment, the lipid profile, serum creatinine level, and urine protein were measured at the beginning of the study and then every year. The fluctuation in HbA1c throughout the period was expressed as the standard deviations (SDs) of all measurements of the HbA1c. Results: The frequency of SMBG was significantly and negatively correlated with the SDs of the HbA1c (r =-0.553, p < 0.001) but not with the average HbA1c. After controlling for age, sex, body mass index, duration of diabetes and comorbidities (dyslipidemia and hypertension), the correlation was still apparent (r =-0.511, p = 0.008). Patients with progression of nephropathy, neuropathy, and retinopathy, exhibited greater fluctuation of HbA1cs (2.38 ± 0.99 vs. 0.93 ± 1.16, p-value 0.002; 0.97 ± 1.59 vs. 0.90 ± 0.56, pvalue 0.04; 0.99 ± 1.33 vs. 0.90 ± 0.56, p-value 0.04, respectively) and less frequent SMBG (3.2 ± 2.6 vs. 4.3 ± 3.1, p-value 0.02; 3.2 ± 2.6 vs. 4.1 ± 3.9, p-value 0.05; 3.0 ± 3.1 vs. 4.2 ± 2.8, p-value 0.01, respectively) than patients without progression of these complications. Conclusion: This study shows that frequent SMBG decreased the fluctuation of HbA1c and decreased microvascular complications. Decreasing fluctuation of HbA1c may play an important role in diabetes treatment.

OBJECTIVE: To identify response shift using two structural equation modeling (SEM) techniques. STUDY DESIGN AND SETTING: Hypertensive patients (n = 909) with coronary artery disease (CAD) completed SF-36 surveys at both baseline and 1-year follow-up. Response shift was identified using Oort and Schmitt SEM techniques. The type of response shift linked to changes in various parameters of the SEM measurement model is defined differently for both SEM approaches. Effect sizes were calculated for the impact of response shift on the change of SF-36 domain scores when using the Oort approach. RESULTS: Both Oort and Schmitt SEM approaches identified response shift only in the SF-36 physical functioning (PF) scale. The effect size of recalibration on the change of PF domain scores when using the Oort approach was -0.12. CONCLUSION: This study showed that hypertensive patients with CAD experienced a response shift over a 1-year period. Both the SEM approaches identified response shift (uniform recalibration using the Oort approach and recalibration using the Schmitt approach); however, both approaches use different parameters to define and test response shift. We found that either the variation in analytic methods or the sample used may influence the identification and type of response shift.

Several studies have investigated how prepared adolescents are to transition to adult health care and barriers to transition for adolescents with special health care needs. The majority of these studies, however, have only assessed these experiences from the parents' point of view. Our study aims to assess the congruence of adolescents and parents reported transition planning and the factors associated with planning. A secondary data analysis was conducted using telephone survey data. Data were collected from parents and adolescents with special health care needs who received health care through Florida's Title V public insurance program. The final sample included 376 matched pairs of adolescent-parent surveys. To assess health care transition planning, respondents were asked if discussions had occurred with the adolescents' doctor, nurse, or with each other. Parents reported higher levels of planning than adolescents. Results show the lowest level of agreement between the parent and adolescent reports (κ < 0.2) and the highest level of agreement when parents and adolescents were asked if they discussed transition with each other (κ = 0.19). Regression results suggest that older adolescents are more prepared (vs. younger) and that adolescents whose parents have lower educational attainment are less prepared for transition. Results from this study suggest that there may be miscommunication around discussions related to transition, although further research is warranted. It is important to ensure that adolescents, not just parents, have a thorough understanding of transition since they will ultimately be responsible for their own health care once they reach adulthood.

PURPOSE: Young adult survivors of childhood cancer (YASCC) are an ever-growing cohort of survivors due to increasing advances in technology. Today, there is a shift of focus to not just ensuring survivorship but also the quality of survivorship, which can be assessed with standardized instruments. The majority of standardized health related quality of life (HRQoL) instruments, however, are non-specific to this age group and the unique late effects within YASCC populations. The purpose of this study was to investigate the relevance and accuracy of standardized HRQoL instruments used with YASCC. METHODS: In a previous study, HRQoL items from several instruments (SF-36, QLACS, QLS-CS) were examined for relevance with a population of YASCC. Participants (n = 30) from this study were recruited for a follow-up qualitative interview to expand on their perceptions of missing content from existing instruments. RESULTS: Respondents reported missing, relevant content among all three of the HRQoL instruments. Results identified three content areas of missing information:(1) Perceived sense of self,(2) Relationships, and (3) Parenthood. CONCLUSIONS: Existing HRQoL instruments do not take into account the progression and interdependence of emotional development impacted by a cancer diagnosis. The themes derived from our qualitative interviews may serve as a foundation for the generation of new items in future HRQoL instruments for YASCC populations. Further testing is required to examine the prevalence, frequency, and breadth of these items in a larger sample.

OBJECTIVES To combine anchor- and distribution-based approaches to identify minimally important differences (MIDs) for the short-form six-dimension utility index (SF-6D) and to identify variables associated with self-reported health status change. DESIGN Descriptive, exploratory, nonexperimental study. SETTING United States between April 1, 1999, and October 31, 1999. PATIENTS 2,317 participants of SADD-Sx (Study of Antihypertensive Drugs and Depressive Symptoms), aged 50 years or older and with hypertension and coronary artery disease. INTERVENTION Patients were randomized into a verapamil SR- or atenolol-led hypertensive treatment strategy and mailed baseline and 1-year surveys. MAIN OUTCOME MEASURE SF-6D utility scores for patients completing both surveys. RESULTS The pooled mean (±SD) MID change on the SF-6D of patients whose health status minimally changed was 0.035 ± 0.095. The anchor-based change scores had a median value of 0.036 (interquartile range -0.03 to 0.10). One-third and one-half of the SD of SF-6D change scores were 0.035 and 0.053, respectively. Whites were less likely to report minimally improved health status compared with nonwhites (odds ratio 0.59 [95% CI 0.40-0.88]). Change in SF-6D scores improved prediction of health status change. CONCLUSION We recommend using the MID range based on all patients combined (-0.03 to 0.10) to interpret SF-6D scores. These estimates can be used in conjunction with other measures of efficacy to determine meaningful changes. SF-6D demonstrates potential utility in predicting minimally important improvement or worsening among patients receiving different pharmacologic medications.

PURPOSE: Few studies examine the relevance of health-related quality of life (HRQOL) instruments for young adult survivors of childhood cancer (YASCC). This study compared the psychometric properties of two survivor-specific instruments, the Quality of Life-Cancer Survivor (QOL-CS) and Quality of Life in Adult Cancer Survivor (QLACS). METHODS: Data from 151 YASCC who enrolled in cancer/tumor registries of two medical centers were used. We examined construct validity by conducting confirmatory factor analysis using indices of chi-square statistic, comparative fit index, and root mean square error of approximation. We examined convergent/discriminant validity by comparing Pearson's correlation coefficients of homogeneous (e.g., physical functioning and pain) of both instruments versus heterogeneous domains (e.g., physical and psychological functioning). We assessed known-groups validity by examining the extent to which HRQOL differed by late effects and comorbid conditions and calculated relative validity (RV) defined as contrasting F-statistics of individual domains to the domain with the lowest F-statistic. Superior known-groups validity is observed if a domain of one instrument demonstrates a higher RV than other domains of the instruments. RESULTS: YASCC data cannot replicate the constructs both instruments intend to measure, suggesting poor construct validity. Correlations of between-homogeneous and between-heterogeneous domains of both instruments were not discernible, suggesting poor convergent/discriminant validity. Both instruments were equally able to differentiate HRQOL between YASCC with and without late effects and comorbid conditions, suggesting similar known-groups validity. CONCLUSIONS: Neither instrument is superior. Item response theory is suggested to select high-quality items from different instruments to improve HRQOL measure for YASCC.

BACKGROUND: Little attention has been paid to selecting and developing health-related quality of life (HRQOL) measurement tools for young adult survivors of childhood cancer (YASCC). The primary purpose of this study was to develop a HRQOL tool for YASCC based on three legacy instruments. METHODS: Data collected from 151 YASCC were analyzed. HRQOL was measured using the Medical Outcomes Study SF-36, Quality of Life in Adult Cancer Survivors, and Quality of Life-Cancer Survivor. We used the following stages to develop our HRQOL tool: mapping items from three instruments into a common HRQOL construct, checking dimensionality using confirmatory factor analyses (CFA), and equating items using Rasch modeling. RESULTS: We assigned 123 items to a HRQOL construct comprised of six generic and eight survivor-specific domains. CFA retained 107 items that meet the assumptions of unidimensionality and local independence. Rasch analysis retained 68 items that satisfied the indices of information-weighted/outlier-sensitive fit statistic mean square. However, items in most domains possess relatively easy measurement properties, whereas YASCC's underlying HRQOL was on the middle to higher levels. CONCLUSIONS: Psychometric properties of the established tool for measuring HRQOL of YASCC were not satisfied. Future studies need to refine this tool, especially adding more challenging items.

Cell surface mucins configure the cell surface by presenting extended protein backbones that are heavily O-glycosylated. The glycopeptide structures establish physicochemical properties at the cell surface that enable and block the formation of biologically important molecular complexes. Some mucins, such as MUC1, associate with receptor tyrosine kinases and other cell surface receptors, and engage in signal transduction in order to communicate information regarding conditions at the cell surface to the nucleus. In that context, the MUC1 cytoplasmic tail (MUC1CT) receives phosphorylation signals from receptor tyrosine kinases and serine/threonine kinases, which enables its association with different signaling complexes that conduct these signals to the nucleus and perhaps other subcellular organelles. We have detected the MUC1CT at promoters of over 500 genes, in association with several different transcription factors, and have shown that promoter occupancy can vary under different growth factor conditions. However, the full biochemical nature of the nuclear forms of MUC1 and its function at these promoter regions remain undefined. I will present evidence that nuclear forms of the MUC1CT include extracellular and cytoplasmic tail domains. In addition, I will discuss evidence for a hypothesis that the MUC1CT possesses a novel catalytic function that enables remodeling of the transcription factor occupancy of promoters, and thereby engages in regulation of gene expression.

Background:  The aim of this study was to identify the prognostic factors of long-term survival, and optimal therapeutic protocol for patients with distant metastasis secondary to differentiated thyroid carcinoma (DTC). Methods:  A retrospective review of 1665 patients with DTC treated at a regional tertiary hospital in Taiwan between 1986 and 2010 was performed. Among them, 207 patients were found to have distant metastasis. For a long-term outcome survey, 126 patients that had received at least 5 years (mean 9.6 ± 5.2 years) of follow-up after the diagnosis of distant metastasis were analyzed for this study. Prognostic factor analysis included age, sex, histology, disease stage, type of surgical procedure, site of metastatic foci,(131) I avidity of tumour, thyroglobulin (Tg) level, and accumulated therapeutic dose of radioiodine. Results:  The mean age at diagnosis of distant metastasis was 46.4 ± 17.2 years. The female-to-male ratio was 2.1:1. The 10- and 15-year survival rates were 70.6% and 64.9%, respectively. The independent predictors of survival were: younger age, surgical dissection of neck lymph nodes (LNs), and low TSH-stimulated Tg level (<400 μg/l) at the discovery of metastasis. Most cases of resolved (131) I-avid disease (79.2%) and disease-free remission (87.5%) received a cumulative dose no greater than 600 mCi of (131) I. The mean cumulative doses of (131) I in both deceased and living patients were similar. Conclusion:  The prognosis of patients with distant metastasis from DTC within this study was found to be favourable. Survival may be improved by surgical dissection of neck lymph nodes, but repeated (131) I therapy greater than 600 mCi is not advised unless there is a high probability that it would benefit the patient.