Publications

HAPE (high-altitude pulmonary oedema) is characterized by pulmonary hypertension, vasoconstriction and an imbalance in oxygen-sensing redox switches. Excess ROS (reactive oxygen species) contribute to endothelial damage under hypobaric hypoxia, hence the oxidative-stress-related genes CYBA (cytochrome b-245 α polypeptide) and GSTP1 (glutathione transferase Pi 1) are potential candidate genes for HAPE. In the present study, we investigated the polymorphisms -930A/G and H72Y (C/T) of CYBA and I105V (A/G) and A114V (C/T) of GSTP1, individually and in combination, in 150 HAPE-p (HAPE patients), 180 HAPE-r (HAPE-resistant lowland natives) and 180 HLs (healthy highland natives). 8-Iso-PGF2α (8-iso-prostaglandin F2α) levels were determined in plasma and were correlated with individual alleles, genotype, haplotype and gene-gene interactions. The relative expression of CYBA and GSTP1 were determined in peripheral blood leucocytes. The genotype distribution of -930A/G, H72Y (C/T) and I105V (A/G) differed significantly in HAPE-p compared with HAPE-r and HLs (P≤0.01). The haplotypes G-C of -930A/G and H72Y (C/T) in CYBA and G-C and G-T of I105V (A/G) and A114V (C/T) in GSTP1 were over-represented in HAPE-p; in contrast, haplotypes A-T of -930A/G and H72Y (C/T) in CYBA and A-C of I105V (A/G) and A114V (C/T) in GSTP1 were over-represented in HAPE-r and HLs. 8-Iso-PGF2α levels were significantly higher in HAPE-p and in HLs than in HAPE-r (P=2.2×10(-16) and 1.2×10(-14) respectively) and the expression of CYBA and GSTP1 varied differentially (P<0.05). Regression analysis showed that the risk alleles G, C, G and T of -930A/G, H72Y (C/T), I105V (A/G) and A114V (C/T) were associated with increased 8-iso-PGF2α levels (P<0.05). Interaction between the two genes revealed over-representation of most of the risk-allele-associated genotype combinations in HAPE-p and protective-allele-associated genotype combinations in HLs. In conclusion, the risk alleles of CYBA and GSTP1, their haplotypes and gene-gene interactions are associated with imbalanced oxidative stress and, thereby, with high-altitude adaptation and mal-adaptation.

OBJECTIVE

To examine the relationship between overuse of healthcare services and geographic variations in medical care.

DESIGN

Systematic Review.

DATA SOURCES

Articles published in Medline between 1978, the year of publication of the first framework to measure quality, and January 1, 2009.

STUDY SELECTION

Four investigators screened 114,830 titles and 2 investigators screened all selected abstracts and articles for possible inclusion and extracted all data.

DATA EXTRACTION

We extracted data on rates of overuse in different geographic areas. We also extracted data on underuse, if available, for the same population in which overuse was measured.

RESULTS

Five papers examined the relationship between geographic variations and overuse of healthcare services. One study in 2008 compared the appropriateness of coronary angiography (CA) for acute myocardial infarction in high-cost areas versus low cost areas in the Medicare population and found largely similar rates of inappropriateness (12.2% vs. 16.2%). A study in 2000 using national data concluded that overuse of CA explained little of the geographic variations in the use of this procedure in the Medicare program. An older study of Medicare patients found similar rates of inappropriate use of CA (15% to 17% vs. 18%), endoscopy (15% vs. 18% 19%), and carotid endarterectomy (29% vs. 30%) in low-use and high-use regions. A small area reanalysis of data from this study of 3 procedures found no evidence of a relationship between inappropriate use of procedures and volume in 23 adjacent counties of California. Another 2008 study found that inappropriate chemotherapy for stage I cancer was less common in low-cost areas compared with high-cost areas (3.1% vs. 6.3%).

CONCLUSIONS

The limited available evidence does not lend support to the hypothesis that inappropriate use of procedures is a major source of geographic variations in intensity and/or costs of care. More research is needed to improve our understanding of the relationship between geographic variations and the quality of care.