Case studies evaluating transdermal continuous oxygen for the treatment of chronic sickle cell ulcers.

OBJECTIVE: Refractory leg ulcerations are common in homozygous sickle cell anemia. In this case series, patients were treated with transdermal continuous oxygen therapy (TCOT), based on the hypothesis that oxygen deprivation caused by arteriovenous shunting may be remedied by providing oxygen directly to the wound bed. The authors believe this is the first attempt to treat sickle cell ulcers with TCOT. CASE PRESENTATION: Five patients with long histories of recurring sickle cell disease ulcers that would not heal with various conventional and/or other adjunctive wound healing modalities were treated with TCOT. The patients had recurring nonhealing wounds for 30, 21, 20, 20, and 15 years, respectively. All 5 patients healed or showed substantial improvement in the treatment periods of 3 to 36 weeks. CONCLUSION: The authors conclude that TCOT may be a novel, effective, and inexpensive modality in treating patients with sickle cell disease ulcers. Improvement was typically noticeable within 2 weeks. Further clinical trials may be considered to evaluate the efficacy of TCOT in sickle cell ulcers.

Echocardiographic findings in patients with sickle cell disease.

Pulmonary hypertension is a complication of sickle cell disease that is associated with increased mortality. Whether this complication is associated with hemolysis has been questioned. Systolic pulmonary artery blood pressure can be estimated from echocardiography-determined tricuspid regurgitation velocity (TRV). A velocity of 2.5 m/s or higher suggests possible pulmonary hypertension. A retrospective review of hospital records from adult patients with sickle cell disease undergoing echocardiography in 2006 and 2007 was performed at a tertiary level hospital. Echocardiographic, demographic, and clinical laboratory data were collected. Echocardiographic results were available for 105 adult sickle cell patients. Of these, 62 (59%) had a TRV ≥2.5 m/s and 24 (22.8%) had a TRV ≥3.0 m/s. Mitral valve regurgitation was observed in 44% and left ventricular abnormalities (defined by either hypertrophy or dilation) in 28% of cases. Elevated TRV had independent and significant associations with greater age, higher serum lactate dehydrogenase (LDH) concentration, and lower hemoglobin concentration. We confirmed that elevated TRV is common among hospital-based adults with sickle cell disease. Significant, independent associations were found with both elevated LDH concentration and degree of anemia, suggesting that hemolytic and other mechanisms contribute to pulmonary hypertension in patients with sickle cell disease.

Potential nonresponse bias in a clinical examination after initial screening using iron phenotyping and HFE genotyping in the hemochromatosis and iron overload screening study.

BACKGROUND: Little is known about the factors affecting participation in clinical assessments after HEmochromatosis and IRon Overload Screening. METHODS: Initial screening of 101,168 primary care patients in the HEmochromatosis and IRon Overload Screening study was performed using serum iron measures and hemochromatosis gene (HFE) genotyping. Using iron phenotypes and HFE genotypes, we identified 2256 cases and 1232 controls eligible to participate in a clinical examination. To assess the potential for nonresponse bias, we compared the sociodemographic, health status, and attitudinal characteristics of participants and nonparticipants using adjusted odds ratios (ORs) and 95% confidence interval (CI). RESULTS: Overall participation was 74% in cases and 52% in controls; in both groups, participation was highest at a health maintenance organization and lowest among those under 45 years of age (cases: OR = 0.68; 95% CI 0.53, 0.87; controls: OR = 0.59; 95% CI 0.44, 0.78). In controls only, participation was also lower among those over 65 years of age than the reference group aged 46-64 (OR = 0.64; 95% CI 0.47, 0.88). Among cases, participation was higher in HFE C282Y homozygotes (OR = 3.98; 95% CI 2.60, 6.09), H63D homozygotes (OR = 2.79; 95% CI 1.23, 6.32), and C282Y/H63D compound heterozygotes (OR = 1.82; 95% CI 1.03, 3.22) than in other genotypes, and lower among non-Caucasians and those who preferred a non-English language than in Caucasians and those who preferred English (p < 0.0001). CONCLUSIONS: Subjects with greatest risk to have iron overload (C282Y homozygotes; cases > or =45 years; Caucasians) were more likely to participate in a postscreening clinical examination than other subjects. We detected no evidence of strong selection bias.

Screening for hemochromatosis and iron overload: satisfaction with results notification and understanding of mailed results in unaffected participants of the HEIRS study.

AIM: The purpose of this study was to assess the level of satisfaction and understanding of test results, by a sample of non-C282Y homozygous participants in the hemochromatosis and iron overload screening (HEIRS) study, who received serum ferritin (SF), transferrin saturation (TS), and HFE gene test results by mail. METHODS: Approximately 1 month after receiving test results by mail, participants were surveyed about understanding of and satisfaction with results notification. RESULTS: Overall, participants were satisfied with receiving test results by mail. Participants receiving results with one or two HFE mutations or TS and/or SF levels outside the normal range (an "alert value") were less likely to be satisfied with this method of notification. Participants with normal HFE test results understood their results and recommendations better than those with one or two mutations. Although all participants received results letters in their native language, English-speaking participants had higher mean understanding scores than Mandarin, Vietnamese, or Spanish-speaking participants. CONCLUSION: Participants were satisfied with receiving test results by mail. However, the level of understanding of the results was not sufficient for this mode of results notification to stand alone, especially for non-English speaking participants, and all participants with one or more test results outside the normal range.

Health-related quality of life in a racially diverse population screened for hemochromatosis: results from the Hemochromatosis and Iron Overload Screening (HEIRS) study.

PURPOSE: The HEIRS Study screened 101,168 primary care participants for iron overload with serum transferrin saturation (TS), serum ferritin (SF), and C282Y and H63D mutations of the HFE gene. The objective of this study was to evaluate the impact of screening on participants' well-being. METHODS: All C282Y homozygotes, participants with an elevated TS and SF concentration, and a control group of phenotype-genotype negative persons, with neither C282Y nor H63D mutations in the HFE gene were recalled for a clinical evaluation. Health-related quality of life was assessed before screening and approximately 1 week after receipt of the results. Health worries were assessed only at follow-up. RESULTS: Participants (N = 1478) completed both initial and follow-up surveys. After adjusting for model covariates, phenotype and genotype combinations were statistically significant predictors of changes in psychological well-being (P = 0.0001) and general health (P = 0.0014). C282Y homozygotes with transient elevations in TS or SF were significantly more likely to worry about their health compared to study controls. Race, ethnicity, and preferred language subgroups differed on psychological well-being, general health, and health worry. CONCLUSION: Iron phenotype and HFE genotype are associated with health-related quality of life. Health worry was greatest among those considered genetically "at risk. " This may have important implications for multi-ethnic population-based screening studies in which genotype and phenotype are communicated.

Predictors of belief that genetic test information about hemochromatosis should be shared with family members.

We queried 101,951 white, Hispanic, black, Asian, American Indian (i.e., American Indian or Alaska Native in the United States and North American Indian, Metis, or Inuit in Canada) and Pacific Islander (including Native Hawaiian) adults who agreed to be genotypically and phenotypically screened for hemochromatosis as part of the Hemochromatosis and Iron Overload Screening (HEIRS) study about their views on sharing genetic test information with family members. Multiple logistic regression (adjusting for study site, age group, race/ethnicity, preferred language, gender, education group, income group, SF-36 General Health and Mental Health subscales, perceived benefits and limitations of genetic testing, and belief that genetic testing is a good idea) evaluated independent predictors of responding "Strongly Agree" or "Agree" versus "Disagree" or "Strongly Disagree" to the statement "Information about a person's genetic risk should be shared with family members". Agreement that genetic risk information should be shared with family members was high (93% in the overall sample of 78,952 who answered this question), but differed among racial/ethnic groups. Hispanics were significantly less likely to agree that genetic test information should be shared with family members (i.e., 88% versus 92% or more among all other ethnicities). The relationship of perceived limitations and benefits of testing, gender, and age group to the belief that information should be shared differed among racial/ethnic groups, with Spanish-preferring Hispanics being the most different from other subgroups.