Adaptation of the robust method to large distributions of reference values: program modifications and comparison of alternative computational methods.

The objective of this research was to compute reference limits using reference values from patients entering pharmaceutical development clinical trials by the nonparametric method and the robust method of Horn and Pesce, with and without outlier exclusion, and compare the methods with respect to influence on the limits. Reference limits were computed for 38 analytes with over 130,000 subjects contributing reference values. Subjects were partitioned into 10 demographic strata for limit computation.

Reference Limits for Outlier Analyses in Randomized Clinical Trials.

Background: Reference limits used in clinical medicine to screen and manage patients are typically developed nonparametrically using reference values from a limited number of healthy subjects using a 95th percentile reference interval. We have evaluated alternative methods of computation and the resulting limits for use in the analyses of treatment-emergent outliers in clinical trials.

Methods: We developed a set of alternative reference limits for 38 laboratory analytes based on alternative statistical methods and assessed their relative performance in clinical trial analysis.

Risk of Advanced Neoplasia Using the National Cancer Institute's Colorectal Cancer Risk Assessment Tool.

Background: There is no validated, discriminating, and easy-to-apply tool for estimating risk of colorectal neoplasia. We studied whether the National Cancer Institute's (NCI's) Colorectal Cancer (CRC) Risk Assessment Tool, which estimates future CRC risk, could estimate current risk for advanced colorectal neoplasia among average-risk persons.

Methods: This cross-sectional study involved individuals age 50 to 80 years undergoing first-time screening colonoscopy.

Prevalence and correlates of pain and pain treatment in a western Kenya referral hospital.

Background: Pain is often inadequately evaluated and treated in sub-Saharan Africa (SSA).

Objective: We sought to assess pain levels and pain treatment in 400 hospitalized patients at a national referral hospital in western Kenya, and to identify factors associated with pain and pain treatment.

Design: Using face-validated Kiswahili versions of two single-item pain assessment tools, the Numerical Rating Scale (NRS) and the Faces Pain Scale-Revised (FPS-R), we determined patients' pain levels.

Health outcomes and cost of care among older adults with schizophrenia: a 10-year study using medical records across the continuum of care.

Objectives: The population of older patients with schizophrenia is increasing. This study describes health outcomes, utilization, and costs over 10 years in a sample of older patients with schizophrenia compared with older patients without schizophrenia.

Methods: An observational cohort study of 31,588 older adults (mean age: 70.

Atopy, cytokine production, and airway reactivity as predictors of pre-school asthma and airway responsiveness.

Background: Childhood asthma is often characterized by recurrent wheezing, airway hyper-reactivity, atopy, and altered immune characteristics; however, our understanding of the development of these relationships from early in life remains unclear. The aim of our study was to evaluate whether atopy, cytokine production by peripheral blood mononuclear cells (PBMCs), and airway responsiveness, assessed in infants and toddlers, are associated with asthma and airway responsiveness at 4-years of age.

Methods: Infants with eczema (N = 116), enrolled prior to wheezing, were assessed at entry (mean age of 10.

Inverse relationship between long-chain n-3 fatty acids and risk of sudden cardiac death in patients starting hemodialysis.

Experimental and clinical evidence suggests that long-chain n-3 fatty acids may protect against sudden cardiac death, the leading cause of mortality in hemodialysis patients. Here we investigated whether long-chain n-3 fatty acids have a protective relationship with sudden cardiac death in 100 patients who died of sudden cardiac death during the first year of starting hemodialysis and 300 patients who survived. Individuals were selected from a nationally representative cohort of over 1000 US hemodialysis units in 2004-2005.

Low blood levels of long-chain n-3 polyunsaturated fatty acids in US hemodialysis patients: clinical implications.

Background: Cardioprotective and other clinical benefits of long-chain n-3 polyunsaturated fatty acids (PUFA) are inversely related to dietary intake and hence blood content. We therefore investigated, in the first study of its kind, the blood content and distribution of these fatty acids in a large representative population of US hemodialysis patients.

Methods: Frozen sera were obtained from 400 individuals who were part of a large, contemporary, representative cohort of US incident hemodialysis patients.

Long-term hematopoietic stem cell damage in a murine model of the hematopoietic syndrome of the acute radiation syndrome.

Residual bone marrow damage (RBMD) persists for years following exposure to radiation and is believed to be due to decreased self-renewal potential of radiation-damaged hematopoietic stem cells (HSC). Current literature has examined primarily sublethal doses of radiation and time points within a few months of exposure. In this study, the authors examined RBMD in mice surviving lethal doses of total body ionizing irradiation (TBI) in a murine model of the Hematopoietic Syndrome of the Acute Radiation Syndrome (H-ARS).

Pericyte coverage of differentiated vessels inside tumor vasculature is an independent unfavorable prognostic factor for patients with clear cell renal cell carcinoma.

Background: The objective of this study was to evaluate the effect of pericyte coverage (PC) of differentiated tumor microvessels on the prognosis of patients with clear cell renal cell carcinoma (CCRCC).

Methods: Samples from 2 cohorts of patients with CCRCC (101 Asian patients and 524 US patients) were prepared using 2 different histologic approaches: routine sectioning versus tissue microarray. Then, the samples were immunohistochemically doubled-stained for a pericyte marker (alpha smooth muscle actin [α-SMA]) and a differentiated vessel marker (cluster of differentiation 34 [CD34]), followed by multispectral image capturing and computerized image analyses to quantify the microvessel density (MVD) and the PC of differentiated vessels.

Pulmonary diffusing capacity in healthy Caucasian children.

Previous studies of pulmonary diffusing capacity in children differed greatly in methodologies; numbers of subjects evaluated, and were performed prior to the latest ATS/ERS guidelines. The purpose of our study was to establish reference ranges for the diffusing capacity to carbon monoxide (DL(CO) ) and alveolar volume (V(A) ) in healthy Caucasian children using current international guidelines and contemporary equipment. Healthy children from the United States (N = 303) and from Australia (N = 176) performed acceptable measurements of single breath pulmonary diffusing capacity and alveolar volume according to current ATS/ERS guidelines.

MCP-1 and IL-8 as pain biomarkers in fibromyalgia: a pilot study.

Objective: Although fibromyalgia (FM) is traditionally a non-inflammatory condition, emerging data also suggest that FM has an immunologic component. Previous studies have reported that peripheral blood concentrations of two chemokines (i.e.