Alcohol drinking patterns and health care utilization in a managed care organization

OBJECTIVE: To estimate the relationship between current drinking patterns and health care utilization over the previous two years in a managed care organization (MCO) among individuals who were screened for their alcohol use. STUDY DESIGN: Three primary care clinics at a large western MCO administered a short health and lifestyle questionnaire to all adult patients on their first visit to the clinic from March 1998 through December 1998. Patients who exceeded the National Institute on Alcohol Abuse and Alcoholism (NIAAA) guidelines for moderate drinking were given a more comprehensive alcohol screening using a modified version of the Alcohol Use Disorders Identification Test (AUDIT). Health care encounter data for two years preceding the screening visit were linked to the remaining individuals who responded to one or both instruments. Using both quantity-frequency and AUDIT-based drinking pattern variables, we estimated negative binomial models of the relationship between drinking patterns and days of health care use, controlling for demographic characteristics and other variables. PRINCIPAL FINDINGS: For both the quantity-frequency and AUDIT-based drinking pattern variables, current alcohol use is generally associated with less health care utilization relative to abstainers. This relationship holds even for heavier drinkers, although the differences are not always statistically significant. With some exceptions, the overall trend is that more extensive drinking patterns are associated with lower health care use. CONCLUSIONS: Based on our sample, we find little evidence that alcohol use is associated with increased health care utilization. On the contrary, we find that alcohol use is generally associated with decreased health care utilization regardless of drinking pattern.     

Hormone replacement therapy after surgery for stage 1 or 2 cutaneous melanoma

A total of 206 women were followed for a minimum of 5 years after primary melanoma surgery to establish if hormone replacement therapy (HRT) adversely affected prognosis. In all, 123 had no HRT and 22 have died of melanoma; 83 had HRT for varying periods and one has died of melanoma. After controlling for known prognostic factors, we conclude that HRT after melanoma does not adversely affect prognosis.     

Increasing mortality rates of common malignancies in Colombia: an emerging problem

BACKGROUND: As a result of a major social and demographic transition, Colombia is currently undergoing major changes in disease-specific mortality rates, including an increasing burden of cancer death. The current article described some aspects of the evolution of cancer mortality in Colombia and, in particular, highlighted the trends for the most common causes of cancer death in Colombia. METHODS: Cancer deaths registered in the national mortality database from 1981-1996 were used to obtain age-standardized mortality rates by gender and site using the world standard population. The estimated annual percentage change was obtained by fitting a simple log-linear model to the rates in the last decade of recorded data, to gauge recent and near-future cancer mortality trends. RESULTS: Between 1987 and 1996, the most common causes of cancer death were gastric carcinoma (17% of all cancer deaths), followed by lung (10.5%), prostate (6.2%), cervical (6%), and colorectal carcinoma (5.4%). There were observed declines in mortality trends noted in both genders for gastric carcinoma. Trends in lung carcinoma appeared to be reaching a plateau among men, but increased among women. There were apparent increases in rates of death from colorectal carcinoma for both genders, and from prostate carcinoma for men. Cervical carcinoma appeared to be increasing moderately. CONCLUSIONS: The authors reported that mortality rates from the most common malignancies are increasing, indicating that effective strategies for cancer control need to be put into immediate practice. To monitor and evaluate future trends, the provision of high-quality data also needs to be addressed.     

PU.1 supports proliferation of immature erythroid progenitors

Despite normal levels of erythropoiesis in PU.1(-/-) embryos, PU.1(-/-) fetal hematopoietic progenitors are unable to establish sustained erythropoiesis in the adult bone marrow. This study demonstrates that PU.1(-/-) fetal erythroid progenitors are synergistically expanded by TPO plus SCF, but not combinations of EPO plus SCF, IL-3 or GM-CSF. The EPO defect is not corrected by a constitutively active variant of EPOR. Microarray analysis identified several candidate PU.1 target genes known to affect cytokine signaling and gene regulation in the erythroid lineage. These data suggest that PU.1 plays an important role in regulating the proliferation of immature erythroid progenitors.     

The serotonin-2A receptor gene locus does not contain common polymorphism affecting mRNA levels in adult brain

The serotonin-2A (HTR2A) receptor is a molecule of particular interest in biological psychiatry, as it is an important target for psychotropic drugs, and altered HTR2A expression has been found in several neuropsychiatric conditions, including depression and schizophrenia. Genetic association has been reported between a synonymous 102T/C polymorphism in the gene encoding HTR2A and a number of clinical phenotypes, including schizophrenia, clozapine response, psychotic symptoms in Alzheimer's disease and certain features of depression. Given that there are no known effects of the 102T/C polymorphism on the structure of the receptor, attention has switched to the possibility that the observations of both altered expression and genetic association point to functional sequence variants that alter expression of the HTR2A gene. Moreover, data have been presented recently suggesting that mRNAs containing the 102T- and C-alleles are differentially expressed. This suggests a direct effect of the variant itself on mRNA levels, or the influence of a distinct regulatory variant, such as the -1438A/G promoter polymorphism, with which it is in perfect linkage disequilibrium. The present study tested this hypothesis by employing a highly accurate quantitative allele- specific primer extension assay to measure the relative expression of brain mRNAs carrying each allele in 23 individuals heterozygous for the 102T/C polymorphism. Comparison between allele ratios derived from genomic DNA and mRNA from several cortical regions revealed that the 102C- and T-alleles are expressed identically. Furthermore, the absence of any interindividual variability in relative mRNA allele ratio suggests that the HTR2A locus is unlikely to contain common polymorphisms or epigenetic modification that alter HTR2A mRNA levels in adult brain, and essentially exclude such phenomena as a potential explanation for the altered expression and genetic associations that have been reported to date.     

A simple assay for determining antiviral activity against Crimean-Congo hemorrhagic fever virus

Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne virus that is emerging as a significant human pathogen in many regions of the world, including Africa, Asia, and Europe. In this report, we describe a simple screening method for discovering new antiviral compounds directed against CCHFV. Antiviral activity was determined by assaying infected SW-13 cells (human adrenal gland carcinoma) for protection from cytopathic effect (CPE). By using an in vitro neutral red uptake assay, we were able to quantitatively measure CPE induced by CCHFV. As a proof of concept, we used this method to evaluate the antiviral activity of ribavirin and a series of structural analogs (ribamidine, 6-azauridine, selenazofurin, and tiazofurin) against four geographically diverse strains of CCHFV. Ribavirin inhibited the replication of CCHFV as reported previously using plaque reduction assays. One drug, ribamidine, showed antiviral activity that was 4.5- to 8-fold less than that of ribavirin, and the other three drugs (6-azauridine, selenazofurin, and tiazofurin) did not show significant antiviral activity. There were no significant differences in drug sensitivities among the CCHFV strains. Development of this simple and reliable assay will potentially allow high-throughput screening for discovering additional antiviral drugs to combat this important public health threat.     

Blood withdrawal and infusion via umbilical catheters: effect on cerebral perfusion and influence of ibuprofen

Withdrawal and infusion of blood via umbilical catheters can affect cerebral blood flow in preterm infants. We compared the effects on cerebral perfusion of 3 ml/kg blood withdrawal and infusion via umbilical arterial (UAC) and venous (UVC) catheters in 16 infants < or =32 weeks gestation, age <24 h, on mechanical ventilation. Near infrared spectroscopy was used to monitor changes in cerebral oxy- and deoxyhemoglobin, total cerebral hemoglobin (an index of cerebral blood volume; CBV) and HbD (an index of cerebral intravascular oxygenation). In 10 infants the study was repeated 1 h after intravenous administration of 10 mg/kg ibuprofen as prophylaxis against PDA. Withdrawal and infusion via the UVC caused significant MABP and concordant HbD and CBV changes. Smaller modifications were seen following blood withdrawal and infusion via the UAC. Ibuprofen attenuated cerebral hemodynamic changes associated with withdrawal, but not infusion, from UAC and UVC.     

Effects of diets enriched in saturated (palmitic), monounsaturated (oleic), or trans (elaidic) fatty acids on insulin sensitivity and substrate oxidation in healthy adults

OBJECTIVE: Diets high in total and saturated fat are associated with insulin resistance. This study examined the effects of feeding monounsaturated, saturated, and trans fatty acids on insulin action in healthy adults. RESEARCH DESIGN AND METHODS: A randomized, double-blind, crossover study was conducted comparing three controlled 4-week diets (57% carbohydrate, 28% fat, and 15% protein) enriched with different fatty acids in 25 healthy men and women. The monounsaturated fat diet (M) had 9% of energy as C18:1cis (oleic acid). The saturated fat diet (S) had 9% of energy as palmitic acid, and the trans fatty acid diet (T) had 9% as C18:1trans. Body weight was kept constant throughout the study. After each diet period, insulin pulsatile secretion, insulin sensitivity index (S(I)) by the minimal model method, serum lipids, and fat oxidation by indirect calorimetry were measured. RESULTS: Mean S(I) for the M, S, and T diets was 3.44 +/- 0.26, 3.20 +/- 0.26, and 3.40 +/- 0.26 x 10(-4) min(-1). microU(-1). ml(-1), respectively (NS). S(I) decreased by 24% on the S versus M diet in overweight subjects but was unchanged in lean subjects (NS). Insulin secretion was unaffected by diet, whereas total and HDL cholesterol increased significantly on the S diet. Subjects oxidized the least fat on the M diet (26.0 +/- 1.5 g/day) and the most fat on the T diet (31.4 +/- 1.5 g/day) (P = 0.02). CONCLUSIONS: Dietary fatty acid composition significantly influenced fat oxidation but did not impact insulin sensitivity or secretion in lean individuals. Overweight individuals were more susceptible to developing insulin resistance on high-saturated fat diets.     

Glutathione-S-transferase genotypes, smoking, and their association with markers of inflammation, hemostasis, and endothelial function: the atherosclerosis risk in communities (ARIC) study

Recent epidemiologic studies suggest that polymorphisms of glutathione-S-transferases M1 and T1 (GSTM1/GSTT1) modify the effects of cigarette smoking on risk of coronary heart disease (CHD). Since GSTs are able to detoxify numerous toxic compounds and products of oxidative stress, it is possible that GST genotypes may also modify the capacity of smoking to invoke a chronic inflammatory response. A cross-sectional analysis, using a subset of participants (n = 989) in a large (n = 15, 792) biracial cohort, was used to evaluate levels of nine markers of inflammation, hemostasis, and endothelial function by different combinations of GST genotypes and cigarette smoking status. Participants with the GSTM1 null (GSTM1-0) genotype and > or = 20 pack-years of smoking had the highest mean levels of CRP, fibrinogen, von Willebrand factor, ICAM-1, and VCAM-1 and lowest mean levels of albumin compared to other combinations of genotype and smoking. However, a formal test for interaction between GSTM1 genotype and smoking was statistically significant only for albumin. By contrast, participants who had the functional GSTT1 genotype (GSTT1-1) and smoked > or = 20 pack-years had the highest mean levels of only CRP and fibrinogen. The results of this study provide some limited evidence that GSTM1 and GSTT1 polymorphisms modify the effect of smoking on inflammation, hemostasis, and endothelial function.