Subclinical rejection in tacrolimus-treated renal transplant recipients

BACKGROUND: Subclinical rejection, defined as histologic acute rejection in the absence of graft dysfunction, has been suggested as a cause of chronic allograft rejection. In cyclosporine-treated patients, the incidence of subclinical rejection 3 months after transplant is reported to be approximately 30%. The intent of our study was to determine the incidence of subclinical rejection in tacrolimus-treated renal allograft recipients. METHODS: We prospectively studied the incidence of subclinical rejection on surveillance biopsies performed 3 months after transplantation in 114 patients transplanted between September 1, 1998 and November 30, 2000. All patients received tacrolimus, mycophenolate mofetil, and prednisone, and 56% received antibody induction. RESULTS: Subclinical rejection was detected in 2.6% of patients (3/114, 95% confidence interval 0.5-7.5%). Borderline changes were detected in 11% (12/114). Subclinical rejections were treated with bolus methylprednisolone. CONCLUSIONS: The incidence of subclinical rejection early after kidney transplantation is extremely low in tacrolimus-treated patients in whom early rejections are aggressively treated, suggesting that surveillance biopsies may not be necessary with this regimen.     

Multicollinearity in prognostic factor analyses using the EORTC QLQ-C30: identification and impact on model selection

Clinical and quality of life (QL) variables from an EORTC clinical trial of first line chemotherapy in advanced breast cancer were used in a prognostic factor analysis of survival and response to chemotherapy. For response, different final multivariate models were obtained from forward and backward selection methods, suggesting a disconcerting instability. Quality of life was measured using the EORTC QLQ-C30 questionnaire completed by patients. Subscales on the questionnaire are known to be highly correlated, and therefore it was hypothesized that multicollinearity contributed to model instability. A correlation matrix indicated that global QL was highly correlated with 7 out of 11 variables. In a first attempt to explore multicollinearity, we used global QL as dependent variable in a regression model with other QL subscales as predictors. Afterwards, standard diagnostic tests for multicollinearity were performed. An exploratory principal components analysis and factor analysis of the QL subscales identified at most three important components and indicated that inclusion of global QL made minimal difference to the loadings on each component, suggesting that it is redundant in the model. In a second approach, we advocate a bootstrap technique to assess the stability of the models. Based on these analyses and since global QL exacerbates problems of multicollinearity, we therefore recommend that global QL be excluded from prognostic factor analyses using the QLQ-C30. The prognostic factor analysis was rerun without global QL in the model, and selected the same significant prognostic factors as before.     

Development and validation of a literacy assessment tool for persons with diabetes

PURPOSE: This research was conducted to develop a valid, reliable, quick, and nonstigmatizing tool for assessing literacy in the healthcare setting. METHODS: The Literacy Assessment for Diabetes (LAD) instrument was developed as a word recognition test composed of 3 graded word lists in ascending difficulty. This literacy test, which was specific to diabetes, measured a patient's ability to pronounce terms that they would encounter during clinic visits and in reading menu and self-care instructions. The majority of the terms were on a 4th-grade reading level, with the remaining words ranging from the 6th-through 16th-grade levels. To assess reliability and validity, the LAD was compared with the Wide Range Achievement Test (WRAT3) and the Rapid Estimate of Adult Literacy in Medicine (REALM) by administering all 3 tests to 203 participants in a test-retest study design. RESULTS: All 3 tests (LAD, REALM, and WRAT3) reliably detected true intrasubject variation in word recognition from test to retest. In addition, LAD measured word recognition ability similar to the REALM and WRAT3. CONCLUSIONS: The LAD is a reliable and valid instrument for measuring literacy in adults with diabetes. It can be administered in 3 minutes or less, and the raw score is scaled to a reading grade level.     

Implications of growth patterns of breast-fed infants for growth references

Among the principal tenets of pediatric nutrition is the expectation that meeting the requirements for essential nutrients by feeding either artificial formulae or human milk results in indistinguishable physiological outcomes. This expectation has not been met. Were this observation confined to functional outcomes related to constituents of human milk not found in formula (e.g. immunological components, hormones and very-long-chain polyunsaturated fatty acids), differences between breast-fed and artificially fed infants would not be surprising. However, differences in growth between breast- and bottle-fed infants who live under favorable conditions were mostly unexpected. Bottle-fed infants demonstrate accelerated growth patterns compared to infants who are breast fed (1, 2). Similarly, differences between the growth of breast-fed infants and established growth references were not anticipated (2–4).     

Circulating lipids and glycaemic control in insulin dependent diabetic children

The prevalence of dyslipidaemia in children with insulin dependent diabetes mellitus (IDDM) and its relation to glycaemic control was studied in a group of 51 diabetic children and a control population of 132 schoolchildren. The prevalence of dyslipidaemia in the fasting state was increased in the diabetic group (39%) compared with control subjects (17%). Serum cholesterol concentration alone was raised in 25% of diabetic subjects while serum cholesterol and triglycerides were raised in 14%, compared with 16% and 0.7% respectively in control subjects. Serum total cholesterol (5.1 v 4.5 mmol/l), low density lipoprotein cholesterol (3.2 v 2.6 mmol/l), non-esterified fatty acids (0.91 v 0.50 mmol/l), and triglycerides (0.94 v 0.76 mmol/l) were higher in diabetic children. Serum total cholesterol, triglycerides, and apolipoprotein (apo)B concentrations increased with worsening control, while serum high density lipoprotein cholesterol and apoA-I concentrations were unaltered. There were also positive correlations between glycated haemoglobin and total cholesterol, triglycerides, and apoB in diabetic children. Thus, abnormalities in circulating lipids are common in young subjects with IDDM but largely disappear if blood glucose concentrations are reasonably controlled.     

Selected sulfhydryl inhibitors capable of inducing immunity against cancer in mice.

Selected sulfhydryl inhibitors show greater toxicity to some animal and human cancers than to normal cells, both clinically and in drug sensitivity tests. Such selected SH inhibitors can induce immunity against cancer in mice, unlike other commonly used antitumor agents. Scanning electron micrographs of the surface of Ehrlich ascites cancer cells treated with the sulfhydryl inhibitors show blunting to absence of microvilli and modification of the surface texture of the cancer cells.     

A national framework for cancer surveillance in the United States

Enhancements to cancer surveillance systems are needed for meeting increased demands for data and for developing effective program planning, evaluation, and research on cancer prevention and control. Representatives from the American Cancer Society, Centers for Disease Control and Prevention, National Cancer Institute, National Cancer Registrars Association, and North American Association of Central Cancer Registries have worked together on the National Coordinating Council for Cancer Surveillance to develop a national framework for cancer surveillance in the United States. The framework addresses a continuum of disease progression from a healthy state to the end of life and includes primary prevention (factors that increase or decrease cancer occurrence in healthy populations), secondary prevention (screening and diagnosis), and tertiary prevention (factors that affect treatment, survival, quality of life, and palliative care). The framework also addresses cross-cutting information needs, including better data to monitor disparities by measures of socioeconomic status, to assess economic costs and benefits of specific interventions for individuals and for society, and to study the relationship between disease and individual biologic factors, social policies, and the environment. Implementation of the framework will require long-term, extensive coordination and cooperation among these major cancer surveillance organizations. We acknowledge the contributions of Ronda Starr, who assisted in the preparation of the tables, the web addresses for the data sources, and the references.