Factors associated with failure to achieve a glycated haemoglobin target of <8.0% in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial.

The aim of this study was to identify the clinical features of participants in the standard therapy arm of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) glycaemia trial who failed to reach the glycated haemoglobin (HbA1c) target. We analysed 4685 participants in the standard therapy arm, comparing participants who reached the HbA1c target of <8.0% with those whose HbA1c level was ≥8.0% 12 months after randomization. Baseline and 12-month clinical characteristics were compared. At 12 months after randomization, 3194 participants had HbA1c <8.0% and 1491 had HbA1c ≥8.0%. Black race [odds ratio (OR) 0.74, 95% confidence interval (CI) 0.61-0.89; p = 0.002], severe hypoglycaemia (OR 0.57, CI 0.37-0.89; p = 0.014) and insulin use (OR 0.51, CI 0.40-0.65; p < 0.001) were associated with failure to reach HbA1c goal at 12 months in the adjusted model. Even with free medications, free visits with clinicians and aggressive titration of medications, >30% of participants in the standard arm of the ACCORD trial had an HbA1c ≥8.0% at 1 year. Participants who were black, had severe hypoglycaemia and were on insulin were more likely to have an above-target HbA1c concentration after 12 months on the standard protocol.

Glycaemia and correlates of patient-reported outcomes in ACCORD trial participants.

AIMS: Post-hoc evaluation of relationships between first-year change in glycaemic control (HbA(1c) ) and change in patient-reported outcomes among ACCORD health-related quality of life (HRQoL) substudy participants. METHODS: Data from 2053 glycaemia-trial subjects were analysed. We assessed physical and mental health status (36-Item Short Form Health Survey, Version-2), symptom count and severity (Diabetes Symptoms Distress Checklist) and treatment satisfaction (Diabetes Treatment Satisfaction Questionnaire). Linear mixed models were used to test relationships between 1-year changes in HbA(1c) and patient reported outcomes sequentially adjusting for correlates (baseline characteristics, baseline patient reported outcomes, treatment assignment, frequency of clinical contact and post-randomization weight change plus new complications). RESULTS: Poorer baseline control of HbA(1c) and cardiovascular disease risk factors predicted greater one-year improvements in treatment satisfaction. Similarly, poorer baseline patient reported outcome scores all individually predicted greater 1-year improvement in that same outcome. Accounting for baseline and post-randomization characteristics and treatment arm, 1-year change in HbA(1c) was unrelated to changes in overall physical or mental health; however, every one percentage-point (10.9 mmol/mol) reduction in HbA(1c) was associated with lower symptom count (ß = 0.599; P = 0.012), lower symptom distress (ß = 0.051; P = 0.001), and higher treatment satisfaction (ß = -2.514; P < 0.001). CONCLUSIONS: Independent of all relevant covariates, better glycaemic control over 1 year was associated with reduced patient-reported diabetes symptoms and symptom distress, and increased treatment satisfaction, but not overall physical and mental health. Further investigation is required to understand the specific psychosocial mechanisms that affect how patients value health and treatments.

The impact of sickle cell trait on glycated haemoglobin in diabetes mellitus.

AIMS: To determine the effect of sickle cell trait on measurement of glycated haemoglobin (HbA(1c)) in African American patients with diabetes mellitus. METHODS: This is a retrospective study including 885 outpatients who underwent HbA(1c) testing. Medical record review and sickle cell trait determinations based on the HbA(1c) assay were performed in African American participants. The relationship between HbA(1c) and serum glucose measurements was analysed. RESULTS: Data were obtained from 385 AA (109 with SCT, 22 with haemoglobin C trait and 254 without haemoglobinopathy) and 500 European American patients. In a model created through multivariate repeated-effects regression, the relationship between HbA(1c) and simultaneous serum glucose did not differ between African American subjects with and without the sickle cell trait, but differed between African American subjects without the sickle cell trait and European Americans (P = 0.0002). CONCLUSIONS: Sickle cell trait does not impact the relationship between HbA(1c) and serum glucose concentration. In addition, it does not appear to account for ethnic difference in this relationship between African Americans and whites.

Ethnic variation in the correlation between random serum glucose concentration and glycated haemoglobin.

AIMS: To determine if the relationship between serum glucose concentration and glycated haemoglobin is different between African-Americans and whites. METHODS: Retrospective cross-sectional study comparing the association between glycated haemoglobin and serum glucose levels, based upon ethnicity. Two databases were evaluated: (i) 4215 African-American and 6359 white outpatients who had simultaneous glycated haemoglobin, random serum glucose and creatinine concentration measurements between 2000 and 2007 at the North Carolina Baptist Hospital and (ii) 1021 white and 312 African-American Diabetes Heart Study (DHS) participants. RESULTS: In North Carolina Baptist Hospital clinic attendees, a given glycated haemoglobin was associated with higher serum glucose concentrations in African-Americans compared with whites. In a multivariate model with glycated haemoglobin as the outcome variable, racial differences remained significant after adjustment for serum glucose, age, gender and kidney function. For individuals with a serum glucose between 5.6 and 8.3 mmol/l, the glucose : glycated haemoglobin ratio was 1.03 +/- 0.16 mmol/l/% in white individuals and 0.99 +/- 0.17 mmol/l/% in African-Americans (P < 0.0001). For a glycated haemoglobin value of 7.0%, there was a 0.98-mmol/l difference in predicted serum glucose concentration in 50-year-old African-American men, relative to white. Results were replicated in the DHS, where in a best-fit linear model, after adjustment for glucose, African-American race was a significant predictor of glycated haemoglobin (P < 0.0001). CONCLUSIONS: African-Americans have higher glycated haemoglobin values at given serum glucose concentrations relative to whites. This finding may contribute to the observed difference in glycated haemoglobin values reported between these race groups.

Multicentric giant cell tumor of bone--a case report and comprehensive review of literature.

Multicentric giant cell tumor of bone is a very rare occurrence, forming less than 1% of all giant cell tumors. A new case report is presented, along with a comprehensive review of the literature.

Analysis strategies for serial multivariate ultrasonographic data that are incomplete.

Ultrasonographic measurement of intima-media thickness in the carotid artery has emerged as an important non-invasive means of assessing atherosclerosis, and has served to define primary outcome measures related to progression of arterial lesions in several large clinical trials and epidemiologic studies. It is characteristic that measurements often cannot be obtained from all sites during repeated examinations. This leads to incomplete multivariate serial data, for which the set and number of visualized sites may vary across time. We have contrasted several conditional and unconditional maximum likelihood analytical approaches, and have evaluated these with a simulation experiment based on characteristics of ultrasound measurements collected during the course of the Asymptomatic Carotid Artery Plaque Study. We examined analyses based on unweighted and generalized least squares regression in which we estimated cross-sectional summary statistics using raw means, unconditional maximum likelihood estimates and full maximum likelihood estimates. Since the genesis of missing data is not fully clear, and since the approaches we examined are based, to some degree, on the assumption that data are missing at random, we also examined the relative impact of deviations from such an assumption on each of the approaches considered. We found that maximum likelihood based approaches increased the expected efficiency of the analysis of serial ultrasound data over ignoring missing data by up to 21 per cent.

Malignant fibrillo-caveolated cell carcinoma of the human intestinal tract.

The ultrastructural features of a peculiar midgut carcinoid, containing cytoplasmic filaments, fibrils, and caveolae, are presented. Because of the morphologic similarities between the tumor cells and the recently described intestinal caveolated cell, it is proposed that the cells of the reported carcinoid represent the malignant counterpart of this new type of cell. The name suggested for this variant of a tumor of the enterochromaffin group of intestinal endocrine cells is malignant fibrillocaveolated cell carcinoma.