Changes to osteoporosis prevalence according to method of risk assessment.

The impact of clinical risk factor-based absolute risk methods on the prevalence of high risk for osteoporotic fracture is unknown. We applied absolute risk methods to 6646 subjects and found that the prevalence of elderly women deemed to be at high risk increased substantially, whereas the overall prevalence was highly dependent on the threshold used to designate high risk. INTRODUCTION: Many groups have advocated using absolute risk methods that incorporate clinical risk factors to target patients for osteoporosis therapy. We examined how the application of such absolute risk classification systems influences the prevalence of those considered to be at high risk for osteoporotic fracture and compared these systems to one based solely on BMD. MATERIALS AND METHODS: Using 6646 subjects from the Canadian Multicentre Osteoporosis Study (CaMos), a prospective, randomly selected, population-based cohort, we assessed three different systems for determining prevalence of high risk for osteoporotic fracture: a BMD-based system; a simplified risk factor system incorporating age, sex, BMD, and two clinical risk factors; and a comprehensive system, incorporating age, sex, BMD, and seven clinical risk factors. The 10-year absolute risks of incident fragility fracture were compared across systems using three different high-risk thresholds. RESULTS: The prevalence of a T score < or = -2.5 was 18.8% (95% CI: 17.7-19.9%) in women and 3.9% (95% CI: 3.0-4.7%) in men. Using a 15% 10-year risk of fracture threshold, the prevalence of women at high risk increased to 46.9% (95% CI: 45.4-48.4) and 42.5% (95% CI: 41.1-43.9) when the comprehensive and simplified risk factor classification systems were used, respectively. Using a 25% 10-year absolute risk threshold, the prevalence of high risk was similar to that of the BMD-based system, whereas the 20% threshold gave intermediate rates. All thresholds analyzed resulted in an increased prevalence of older women at high risk for fracture, whereas only the 15% 10-year risk of fracture threshold resulted in an increase in the prevalence of men at high risk. CONCLUSIONS: The application of risk factor-based systems results in an increased prevalence of older women at high risk. The prevalence of individuals at high risk may increase with changes to the methods used to determine those who are eligible for therapy. These data have important implications for the pattern of care and costs of treating osteoporotic fractures.     

Toward a VA women’s health research agenda: Setting evidence-based priorities to improve the health and health care of women veterans

The expansion of women in the military is reshaping the veteran population, with women now constituting the fastest growing segment of eligible VA health care users. In recognition of the changing demographics and special health care needs of women, the VA Office of Research & Development recently sponsored the first national VA Women’s Health Research Agenda-setting conference to map research priorities to the needs of women veterans and position VA as a national leader in Women’s Health Research. This paper summarizes the process and outcomes of this effort, outlining VA’s research priorities for biomedical, clinical, rehabilitation, and health services research.     

The effects of literacy and education on the quantitative and qualitative aspects of semantic verbal fluency.

Semantic verbal fluency tasks are commonly used in neuropsychological assessment. Investigations of the influence of level of literacy have not yielded consistent results in the literature. This prompted us to investigate the ecological relevance of task specifics, in particular, the choice of semantic criteria used. Two groups of literate and illiterate subjects were compared on two verbal fluency tasks using different semantic criteria. The performance on a food criterion (supermarket fluency task), considered more ecologically relevant for the two literacy groups, and an animal criterion (animal fluency task) were compared. The data were analysed using both quantitative and qualitative measures. The quantitative analysis indicated that the two literacy groups performed equally well on the supermarket fluency task. In contrast, results differed significantly during the animal fluency task. The qualitative analyses indicated differences between groups related to the strategies used, especially with respect to the animal fluency task. The overall results suggest that there is not a substantial difference between literate and illiterate subjects related to the fundamental workings of semantic memory. However, there is indication that the content of semantic memory reflects differences in shared cultural background--in other words, formal education--, as indicated by the significant interaction between level of literacy and semantic criterion.     

The mechanism of aphidicolin bioinactivation by rat liver in vitro systems

1. Aphidicolin is shown to undergo rapid metabolism by rat-liver microsomes resulting in its inactivation and loss of its DNA polymerase alpha/delta inhibition. Metabolism of aphidicolin was not observed with cytosolic enzymes of rat liver and was inconsistent with the involvement of microsomal 3 alpha-hydroxysteroid oxidoreductases. 2. Rates of aphidicolin inactivation as a function of microsomal enzyme induction (per nmol cytochrome P-450) followed the order: untreated microsomes greater than dexamethasone-induced greater than phenobarbital-induced greater than beta-naphthoflavone-induced greater than clofibrate-induced. 3. The principal metabolic process, constituting greater than 90% of the metabolic profile, produces 3-ketoaphidicolin 2, which exhibits approximately 10% of the activity of aphidicolin in inhibition of DNA polymerase alpha. This metabolic transformation, the oxidation of an alcohol to a ketone, is an unusual, but not unique conversion, for cytochrome P-450. 4. 3-Ketoaphidicolin 2 is an intermediate and ultimately undergoes 18-dehydroxymethylation to produce 18-noraphidicolinones 3, which are inactive in the inhibition of DNA polymerase alpha. 5. A specific constitutive cytochrome P-450 isozyme, involved in endogenous steroid regulation, was implicated as the species responsible for aphidicolin metabolism in vitro.     

Growth suppression in the Trichuris dysentery syndrome

The Trichuris Dysentery Syndrome (Ramsey, 1962) is an insidious, chronic condition which has clinical features similar to Crohn's ileocolitis and ulcerative colitis, diseases similarly associated with growth retardation. The attained heights and weights of 19 children at the time of diagnosis of intens, -2.4 Standard Deviation (Z) scores from the Tanner-Whitehouse median with weight, adjusted for height-age, -1.3 Z. We present data on the growth velocities of 11 of the children in the half-year following worm expulsion by mebendazole. These children returned to their home environments without food supplementation or close follow-up, but showed an average height velocity of +5.5 Z and weight velocity (for height-age) of +2.4 Z. Of 8 children with unequivocal height spurts only 3 had any weight spurt. We suggest that the pattern of catch-up growth points to the existence of some specific link between allergy or inflammation in the lower intestinal tract and suppression of linear growth, rather than to stunting due to general deprivation and undernutrition.     

HLA-DR 52- and 51-associated DRB1 alleles in Kenya, East Africa

The genes of the major histocompatibility complex (MHC) are amongst the most polymorphic loci known in the human population. The population genetics of the MHC encoded HLA loci of sub-Saharan Africa are of major interest because of their particular genetic diversity. Here we report on the HLA-DR 52- and 51-associated determinants of the DRB1 loci observed in 165 East African individuals studied in Nairobi, Kenya. The HLA-DR typing was done by serologic and by molecular DNA techniques (PCR-SSOP). The most frequent allele identified was DRB1*1101, followed by DRB1*1503 and DRB1*1302. Some unexpected alleles were repeatedly identified: DRB1*1108, DRB1*1316 and DRB1*1421. Most oftheDR 52-and 51-associated DRB1 alleles were correctly identified by serology as part of the DR3, DR5, DR6 and DR2 groups respectively. The HLA-DRB1 profile reported here corroborates previous genetic and linguistic data supporting the concept that the Eastern African Black population is genetically distinct from other African Black populations. This has important implications in public health issues related to the genetic profile of a population (transplantation, vaccine design for example).     

Influence of dietary fiber on insulin receptors in rat intestinal mucosa.

This study was designed to determine the effect of dietary carbohydrate and fiber on mucosal insulin receptors, in order to correlate changes in cellular proliferation with hormonal responsiveness. In two protocols insulin binding was significantly affected by the consumption of dietary fiber. Compared to fiber-free, feeding corn bran increased binding in the duodenum 30% and ileum 50% but decreased binding in the jejunum 44%, and feeding guar gum increased binding in the colon 73% but decreased binding in the jejunum 40%. Feeding wheat bran or oat bran increased binding 50% in the small intestine compared to cellulose or fiber-free. Receptor autophosphorylation was 30% higher with fiber-free or wheat bran feeding than cellulose or oat bran. These changes in receptor binding and activity may correlate with altered rates of cell proliferation induced by dietary fiber.     

Active and passive surveillance for communicable diseases in child care facilities, Seattle-King County, Washington.

OBJECTIVES: The purpose of this study was to develop and evaluate models for public health surveillance of illnesses among children in out-of-home child care facilities. METHODS: Between July 1992 and March 1994, 200 Seattle-King County child care facilities participated in active or enhanced passive surveillance, or both. Reporting was based on easily recognized signs, symptoms, and sentinel events. Published criteria were used in evaluating surveillance effectiveness, and notifiable disease reporting of participating and nonparticipating facilities was compared. RESULTS: Neither surveillance model was well accepted by child care providers. Enhanced passive and active surveillance had comparable sensitivity. Reporting delays and the large amount of time needed for data entry led to problems with timeliness, especially in terms of written reporting during active surveillance. CONCLUSIONS: Widespread active public health surveillance in child care facilities is not feasible for most local health departments. Improvements in public health surveillance in child care settings will depend on acceptability to providers.