A method for measuring interrater agreement on checklists

A method for measuring interrater agreement on checklists is presented. This technique does not assign individual scores to raters, but computes a single agreement score from the concordance of their check mark configurations. An overall coefficient of agreement, called phi, is derived. The agreement coefficient that is expected by chance and the statistical significance of phi are determined by statistical simulation. Despite the dichotomous nature of the checklist agreement (raters either agree or disagree on items), we show that the binomial distribution does not provide a means for testing the statistical significance of phi. A medical education study is used to illustrate the phi methodology.     

Diabetic retinopathy in a black population: the Barbados Eye Study.

OBJECTIVE: The distribution of diabetic retinopathy in black populations is largely unknown. The authors present retinopathy data from the predominately black participants of the Barbados Eye Study (BES). DESIGN AND PARTICIPANTS: Prevalence study of 4631 participants based on a random sample of the Barbados population 40 to 84 years of age (84% participation). MAIN OUTCOME MEASURES: Diabetes was defined as self-reported history of physician-diagnosed diabetes or glycosylated hemoglobin greater than 10% (>2 standard deviations above the population mean of persons without a diabetes history). Retinopathy was assessed by independent gradings of 30 degrees color stereo fundus photographs of the disc and macula. RESULTS: Diabetes was present in 19.4% of black (n = 4314), 15.2% of mixed (black and white; n = 184), and 7.5% of white/other (n = 133) self-reported racial groups. In the black/mixed population, regardless of diabetes status, the prevalence of retinopathy was 5.9%. In the 636 black and mixed participants with diabetes, the prevalence of retinopathy was 28.5%: 19.8% had minimum changes, 7.7% had moderate changes, and 0.9% had severe retinopathy. Clinically significant macular edema (CSME) was found in 8.6% of those with diabetes. CONCLUSIONS: In the population of African origin, approximately 1 in 17 persons had retinopathy. Among those with diabetes, 28.5% had retinopathy and 8.6% had CSME. These results highlight the clinical and public health relevance of diabetic retinopathy in the black population.     

Development and validation of the Diabetes Care Profile

To determine the reliability and the validity of the Diabetes Care Profile (DCP), an instrument that assesses the social and psychological factors related to diabetes and its treatment, two studies with separate populations and methodologies were conducted. In the first study, the DCP was administered to, and physiologic measures collected from, individuals with diabetes being cared for in a community setting (n = 440). In the second study, the DCP and several previously validated scales were administered to individuals with diabetes receiving care at a university medical center (n = 352). Cronbach's alphas of individual DCP scales ranged from .60 to .95 (Study 1) and from .66 to .94 (Study 2). Glycohemoglobin levels correlated with three DCP scales (Study 1). Several DCP scales discriminated among patients with different levels of disease severity. The results of the studies indicate that the DCP is a reliable and valid instrument for measuring the psychosocial factors related to diabetes and its treatment.     

Further studies on the action of 5-hydroxytryptamine on lumbar motoneurones in the rat isolated spinal cord

Summary Using the hemisected spinal cord of the neonate rat, the effects of altered external Ca, thyrotrophin-releasing hormone (TRH) and a number of antagonists were tested on depolarizations evoked by 5-hydroxytryptamine (5-HT). Responses of populations of motoneurones were recorded via a ventral root. 5-Hydroxytryptamine depolarizations were not Ca-dependent but were enhanced in amplitude in Ca-free solutions. Raised Mg reversed this enhancement. 5-Hydroxytryptamine depolarizations persisted in the presence of Mn (1.53 mmol/l). TRH depolarized motoneurones; there was no evidence of modulation of 5-HT responses on concurrent application of TRH. Ritanserin (0.1 mol/l) had a modest blocking action on 5-hydroxytryptamine depolarizations reducing the maximum; 1mol/l ritanserin caused a greater antagonism which was unsurmountable (pIC₅₀ 5.2). Ritanserin (0.1 or 1 mol/l) did not depress responses to noradrenaline (NA). Ketanserin (0.1 mol/l) caused a blockade of slow onset, equilibrium with the receptors requiring 1 h. Blockade by 0.01, 0.1 and 1 mol/l ketanserin was concentration-dependent (pIC₅₀ 6.2). Ketanserin 1 mol/l, but not at lower concentrations, depressed noradrenaline responses. Mianserin (0.1 mol/l) also caused a blockade of slow onset; 0.1 or 1 mol/l produced a flattening of the 5-hydroxytryptamine concentration-response curve but did not depress noradrenaline responses (pIC₅₀ 4.7). The pIC₅₀ for spiperone was 8.0. DOI (10–100 mol/l) had no detectable agonist action but at concentrations of 0.01 and 0.1 mol/l it acted as an antagonist. Equilibration with the receptors occurred over 2 h. DOI (0.01 mol/l) depressed 5-hydroxytryptamine but not noradrenaline responses; higher concentrations of DOI also depressed noradrenaline responses. The pharmacological profile of the 5-hydroxytryptamine receptor mediating depolarization of spinal and facial motoneurones suggests that it belongs to the 5-HT_1C-5-HT₂, group of 5-hydroxytryptamine receptors but is not identical to 5-HT_1C or the 5-HT₂ CNS binding sites. Alternatively, the response might arise from a mixed population of 5-HT₁-like and 5-HT₂ receptors. Send offprint requests to D. I. Wallis at the above address     

Nutritional management of children and adolescents with insulin-dependent diabetes mellitus: a review by the diabetes care and education dietetic practice group

Although individuals with insulin-dependent diabetes mellitus (IDDM) represent only a small proportion of the total number of persons with diabetes, IDDM is one of the most prevalent chronic childhood diseases. The goals of management in IDDM include normal growth and development, control of blood glucose, maintenance of optimal nutritional status, and prevention of complications. Insulin replacement is the mainstay of treatment in IDDM; however, optimal therapy requires a careful balance of food, insulin, and physical activity. To our knowledge, this is the first comprehensive nutrition review of IDDM that emphasizes research specifically in the area of IDDM (vs non-insulin-dependent diabetes mellitus), including data on children and adolescents when available. the process of nutrition education utilizes a staged approach beginning with "survival" information and progressing to in-depth or continuing education and counseling. Important considerations should be to guide the child/adolescent to a meal plan that fits individual life-style, promotes optimal compliance, and advances the goals of management. Throughout the diabetes nutrition education process, the dietitian can positively affect the lives of children/adolescents and their families. More research is needed to better define ways of meeting the nutrition needs of children and adolescents with IDDM in the areas of fiber and glycemic control, fish oil and lipids, sodium and hypertension, and weight control.     

Volunteers at risk.

An experiment is described in which three male volunteers, who fully understood the nature of the project, were given doses of heroin which could have led to addiction if the subjects had proved to be physiologically or psychologically vulnerable to developing a state of addiction. The experiment was discussed most carefully by the Ethics Committee of the unit where it was conducted, and the subjects were themselves the investigators. The objective was to learn about the initial stages of the adaptation to heroin, of which nothing was known as heroin addicts usually come to the doctor when the habit is firmly established. A physician, who has studied the subject of drug addiction in a special clinic, is the first commentator, the second a lawyer and the third an associate professor of social ethics. These three experts are not discussing the results or the methodology of the experiment but whether the decision of the Ethics Committe was the right one.     

Cd36 and molecular mechanisms of insulin resistance in the stroke-prone spontaneously hypertensive rat

Insulin resistance is of pathogenic importance in several common human disorders including type 2 diabetes, hypertension, obesity and hyperlipidemia, but the underlying mechanisms are unknown. The spontaneously hypertensive rat (SHR) is a model of these human insulin resistance syndromes. Quantitative trait loci (QTLs) for SHR defects in glucose and fatty acid metabolism, hypertriglyceridemia, and hypertension map to a single region on rat chromosome 4. Genetic analysis of an SHR derived from a National Institutes of Health colony led to the identification of a causative mutation in the SHR Cd36. We have investigated glucose and fatty acid metabolism in the stroke-prone SHR (SHRSP). We demonstrate defects in insulin action on 2-deoxy-D-glucose transport (SHRSP 3.3 +/- 1.5 vs. 21.0 +/- 7.4 pmol x min(-1) x [20 microl packed cells](-1), SHRSP vs. WKY, respectively, P = 0.01) and inhibition of catecholamine-stimulated lipolysis (P < 0.05 at all concentrations of insulin) in adipocytes isolated from SHRSP. In contrast, basal levels of catecholamine-stimulated nonesterified free fatty acid (NEFA) release and plasma levels of NEFA are similar in SHRSP and WKY. These results are in agreement with the data on the SHR.4 congenic strain, which suggested that the QTL containing Cd36 mutations accounted for the entire defect in basal catecholamine action but only for approximately 40% of the SHR defect in insulin action. In the SHR, both abnormalities appear consequent of defective Cd36 expression. Because Cd36 sequence and expression are apparently normal in SHRSP, it is likely that the molecular mechanism for defective insulin action in this strain is caused by a gene(s) different than Cd36.     

Airborne Infection with Bacillus anthracis��from Mills to Mail

The lack of identified exposures in 2 of the 11 cases of bioterrorism-related inhalation anthrax in 2001 raised uncertainty about the infectious dose and transmission of Bacillus anthracis. We used the Wells-Riley mathematical model of airborne infection to estimate 1) the exposure concentrations in postal facilities where cases of inhalation anthrax occurred and 2) the risk for infection in various hypothetical scenarios of exposure to B. anthracis aerosolized from contaminated mail in residential settings. These models suggest that a small number of cases of inhalation anthrax can be expected when large numbers of persons are exposed to low concentrations of B. anthracis. The risk for inhalation anthrax is determined not only by bacillary virulence factors but also by infectious aerosol production and removal rates and by host factors.     

PDGFRA mutations in gastrointestinal stromal tumors: frequency, spectrum and in vitro sensitivity to imatinib.

PURPOSE: Gastrointestinal stromal tumors (GISTs) commonly harbor oncogenic mutations of the KIT tyrosine kinase, which is a target for the kinase inhibitor imatinib. A subset of GISTs, however, contains mutations in the homologous kinase platelet derived growth factor receptor alpha (PDGFRA), and the most common of these mutations is resistant to imatinib in vitro. Little is known of the other types of PDGFRA mutations that occur in GISTs. MATERIALS AND METHODS: We determined the KIT and PDGFRA mutation status of 1,105 unique GISTs using a combination of denaturing high-performance liquid chromatography and direct sequencing. RESULTS: 66 in exon 18, 11 in exon 12, and three in exon 14. Transient expression of representative PDGFRA isoforms in CHO cells revealed imatinib sensitivity of exon 12 mutations (SPDHE566-571R and insertion ER561-562) and an exon 14 substitution (N659K). However, most isoforms with a substitution involving codon D842 in exon 18 (D842V, RD841-842KI, DI842-843IM) were resistant to the drug, with the exception of D842Y. Interestingly, other mutations in exon 18 (D846Y, N848K, Y849K and HDSN845-848P) were all imatinib sensitive. Proliferation studies with BA/F3 cell lines stably expressing selected PDGFRA mutant isoforms supported these findings. CONCLUSION: Including our cases, there are 289 reported PDGFRA-mutant GISTs, of which 181 (62.6%) had the imatinib-resistant substitution D842V. However, our findings suggest that more than one third of GISTs with PDGFRA mutations may respond to imatinib and that mutation screening may be helpful in the management of these tumors.