The novel toluidine sulphonamide EL102 shows pre-clinical in vitro and in vivo activity against prostate cancer and circumvents MDR1 resistance.

BACKGROUND: Taxanes are routinely used for the treatment of prostate cancer, however the majority of patients eventually develop resistance. We investigated the potential efficacy of EL102, a novel toluidine sulphonamide, in pre-clinical models of prostate cancer. METHODS: The effect of EL102 and/or docetaxel on PC-3, DU145, 22Rv1 and CWR22 prostate cancer cells was assessed using cell viability, cell cycle analysis and PARP cleavage assays. Tubulin polymerisation and immunofluorescence assays were used to assess tubulin dynamics. CWR22 xenograft murine model was used to assess effects on tumour proliferation. Multidrug-resistant lung cancer DLKPA was used to assess EL102 in a MDR1-mediated drug resistance background. RESULTS: EL102 has in vitro activity against prostate cancer, characterised by accumulation in G2/M, induction of apoptosis, inhibition of Hif1α, and inhibition of tubulin polymerisation and decreased microtubule stability. In vivo, a combination of EL102 and docetaxel exhibits superior tumour inhibition. The DLKP cell line and multidrug-resistant DLKPA variant (which exhibits 205 to 691-fold greater resistance to docetaxel, paclitaxel, vincristine and doxorubicin) are equally sensitive to EL102. CONCLUSION: EL102 shows potential as both a single agent and within combination regimens for the treatment of prostate cancer, particularly in the chemoresistance setting.

Purification and identification of a 7.6-kDa protein in media conditioned by superinvasive cancer cells.

BACKGROUND: Selection of the human drug sensitive and invasive cell line (MDA-MB-435S-F) with the chemotherapeutic agent paclitaxel, resulted in the development of drug resistant cell lines displaying enhanced invasion-related characteristics. MATERIALS AND METHODS: Serum-free conditioned media from the human cancer drug-sensitive and invasive cell line (MDA-MB-435S-F) and its paclitaxel-resistant superinvasive variant (MDA-MB-435S-F/Taxol10p4pSI) were analyzed using Surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). RESULTS: A differentially expressed protein was observed at 7.6 kDa, which was 4-fold up-regulated in MDA-MB-435S-F/Taxol10p4pSI. The differentially expressed protein was identified using matrix-assisted laser desorption ionization tandem time-of-flight mass spectrometry (MALDI-TOF/TOF MS), as a fragment of bovine transferrin. The transferrin receptor was also found to be overexpressed in the superinvasive cell line. CONCLUSION: Cleavage of serum proteins such as transferrin could provide a valuable source of markers for malignant tumours and could also play a role in aspects of cancer pathogenesis, such as tumour cachexia.

Increased incidence of infectious diseases during prospective follow-up of human T-lymphotropic virus type II- and I-infected blood donors. Retrovirus Epidemiology Donor Study.

BACKGROUND: To determine whether human T-lymphotropic virus type II (HTLV-II) infection is associated with an increased incidence of bacterial infections, we prospectively observed cohorts of HTLV-I- and HTLV-II-infected and seronegative subjects in 5 US cities. METHODS: Of 1340 present and former blood donors examined at enrollment, 1213 (90.5%) were re-examined after approximately 2 years, including 136 HTLV-I- and 337 HTLV-II-seropositive subjects and 740 demographically stratified HTLV-seronegative subjects. All subjects were seronegative for human immunodeficiency virus. Odds ratios (ORs) for incident disease outcomes were adjusted for covariates, including age, sex, race or ethnicity, education, and, if significantly associated with the outcome, blood center, donation type, income, smoking, alcohol intake, and injected drug use. RESULTS: Compared with seronegative status, HTLV-II infection was associated with an increased incidence of bronchitis (OR, 1.81; 95% confidence interval [CI], 1.20-2.75), bladder and/or kidney infection (OR, 1.94; 95% CI, 1.26-2.98), oral herpes infection (OR, 9.54; 95% CI, 3.33-27.32), and a borderline increased incidence of pneumonia (OR, 2.09; 95% CI, 0.92-4.76); HTLV-I infection was associated with an increased incidence of bladder and/or kidney infection (OR, 2.79; 95% CI, 1.63-4.79). One incident case of HTLV-I-positive adult T-cell leukemia was observed (incidence, 348 per 100,000 HTLV-I person-years), and 1 case of HTLV-II-positive tropical spastic paraparesis-HTLV-associated myelopathy was diagnosed (incidence, 140 per 100,000 HTLV-II person-years). CONCLUSIONS: These data support an increased incidence of infectious diseases among otherwise healthy HTLV-II- and HTLV-I-infected subjects. They are also consistent with the lymphoproliferative effects of HTLV-I, and with neuropathic effects of HTLV-I and HTLV-II.

Colorectal cancer and folate status: a nested case-control study among male smokers.

Evidence is accumulating that folate, a B vitamin found in green leafy vegetables, may affect the development of neoplasia. We examined the relationship between folate status and colorectal cancer in a case-control study nested within the Alpha-Tocopherol Beta-Carotene Study cohort of male smokers 50-69 years old. Serum folate was measured in 144 incident cases (91 colon, 53 rectum) and 276 controls matched to cases on baseline age, clinic, and time of blood collection. Baseline dietary folate was available from a food-use questionnaire for 386 of these men (92%). Conditional logistic regression modeling was used. No statistically significant association was observed between serum folate and colon or rectal cancer. Although a 2-fold increase in rectal cancer risk was suggested for men with serum folate > 2.9 ng/ml and those in the highest quartile of energy-adjusted folate intake, there was no evidence of a monotonic dose-response, and all confidence intervals included unity. For dietary folate and colon cancer, odds ratios of 0.40 [95% confidence interval (CI), 0.16-0.96], 0.34 (95% CI, 0.13-0.88), and 0.51 (95% CI, 0.20-1.31) were obtained for the second through fourth quartiles of energy-adjusted folate intake, respectively, compared to the first (P for trend = 0.15). Furthermore, men with a high-alcohol, low-folate, low-protein diet were at higher risk for colon cancer than men who consumed a low-alcohol, high-folate, high-protein diet (OR, 4.79; 95% CI, 1.36-16.93). This study suggests a possible association between low folate intake and increased risk of colon cancer (but not rectal cancer) and highlights the need for further studies that measure dietary folate and methionine, along with biochemical measures of folate (i.e., erythrocyte and serum), homocysteine, and vitamin B12.

Laboratory abnormalities in former blood donors seropositive for human T-lymphotropic virus types 1 and 2: a prospective analysis.

CONTEXT: The human T-lymphotropic viruses types 1 and 2 (HTLV-1 and HTLV-2) are highly prevalent among injection drug users in the United States. However, the clinical course of infection has not been well characterized. OBJECTIVE: To understand HTLV-1-and HTLV-2-associated laboratory abnormalities, which may provide insights into their underlying pathophysiology. DESIGN: Cohort study. SETTING: Five US blood centers. PARTICIPANTS: A total of 133 HTLV-1-and 332 HTLV-2-seropositive former blood donors and 717 HTLV-seronegative donors followed up prospectively since 1991. MAIN OUTCOME MEASURES: Selected serum chemistry tests and complete blood cell counts were analyzed at enrollment and approximately 2 years later in participants. Repeated-measures analyses were conducted to evaluate the effect of HTLV infection on laboratory measures. RESULTS: Compared with seronegative subjects, HTLV-1-seropositive subjects had 13% higher creatine kinase (P =.02) and slightly elevated lactate dehydrogenase (P =.03) levels at follow-up. The HTLV-2-seropositive participants had 11% higher absolute lymphocyte counts than seronegative subjects (P =.0001). Infection with HTLV-2 also appeared to be associated with slightly higher hemoglobin levels (P =.03) and hematocrit (P =.03) and with lower albumin levels (P =.01). CONCLUSIONS: These results further our understanding of the biological mechanisms underlying HTLV and suggest that HTLV-associated laboratory changes are unlikely to alter clinical evaluation or counseling of otherwise healthy HTLV-infected subjects.

MicroRNA-106b-25 cluster expression is associated with early disease recurrence and targets caspase-7 and focal adhesion in human prostate cancer.

The miR-106b-25 microRNA (miRNA) cluster is a candidate oncogene in human prostate cancer. Here, we report that miRNAs encoded by miR-106b-25 are upregulated in both primary tumors and distant metastasis. Moreover, increased tumor miR-106b expression was associated with disease recurrence and the combination of high miR-106b and low CASP7 (caspase-7) expressions in primary tumors was an independent predictor of early disease recurrence (adjusted hazard ratio=4.1; 95% confidence interval: 1.6-12.3). To identify yet unknown oncogenic functions of miR-106b, we overexpressed it in LNCaP human prostate cancer cells to examine miR-106b-induced global expression changes among protein-coding genes. The approach revealed that CASP7 is a direct target of miR-106b, which was confirmed by western blot analysis and a 3'-untranslated region reporter assay. Moreover, selected phenotypes induced by miR-106b knockdown in DU145 human prostate cancer cells did not develop when both miR-106b and CASP7 expression were inhibited. Further analyses showed that CASP7 is downregulated in primary prostate tumors and metastatic lesions across multiple data sets and is by itself associated with disease recurrence and disease-specific survival. Using bioinformatics, we also observed that miR-106b-25 may specifically influence focal adhesion-related pathways. This observation was experimentally examined using miR-106b-25-transduced 22Rv1 human prostate cancer cells. After infection with a miR-106b-25 lentiviral expression construct, 22Rv1 cells showed increased adhesion to basement membrane- and bone matrix-related filaments and enhanced soft agar growth. In summary, miR-106b-25 was found to be associated with prostate cancer progression and disease outcome and may do so by altering apoptosis- and focal adhesion-related pathways.

Does prevalence of transfusion-transmissible viral infection reflect corresponding incidence in United States blood donors?

BACKGROUND: Calculation of viral residual risk is dependent on estimating incidence, which is not easily obtainable by most blood centers. Prevalence, however, is readily available. Understanding whether prevalence reflects corresponding incidence may help blood centers monitor disease risks. STUDY DESIGN AND METHODS: With data on 12 million allogeneic donations, prevalence and incidence of transfusion-transmitted viral infections (TTVIs) were calculated. Relationships between prevalence (in total, first-time, and repeat donations) and incidence were analyzed for human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) relative to temporal and donor demographic stratifications, respectively. RESULTS: Overall prevalence of HIV, HBV, and HCV did not consistently reflect corresponding incidence. The relationship between prevalence and incidence varied with time and donors' age and was virus-specific. CONCLUSION: Incidence of TTVIs cannot be easily predicted from overall prevalence. Accurate assessment of TTVI risk necessitates knowledge about donation histories and person-years at risk. Establishing comprehensive frameworks for monitoring blood donations and infectious disease markers remains a key to monitoring blood safety.

First year donation patterns predict long-term commitment for first-time donors.

BACKGROUND AND OBJECTIVES: Converting first-time donors to become regular donors continues to be a challenge facing blood centres. We examined whether first-time donors with frequent return in the first 12 months were more likely to become regular donors. SUBJECTS AND METHODS: The donation histories of 179 409 community whole-blood donors, whose first-time donation in 1991 was negative on donor screening tests, were evaluated. Donors were categorized by the number of donations made in the 12 months after (and including) their first donation. The donor return pattern in the subsequent 6 years, and its association with first-year donation frequency and demographics, was evaluated by using logistic regression analysis. A 'regular donor' was defined as one who returned to donate in at least 4 of the 6 years of follow-up. RESULTS: First-year donation frequency was significantly correlated with long-term donor return (P < 0.0001). Among those giving 1, 2, 3, 4 and > or = 5 donations in the first year, 4%, 11%, 21%, 32% and 42%, respectively, became regular donors (P < 0.0001). Similar associations between donation pattern and donor return behaviour were observed after adjusting for demographic variables (P < 0.0001). CONCLUSIONS: Strategies aimed at encouraging current donors to donate more frequently during the first year may help to establish a regular donation behaviour.

The RADAR repository: a resource for studies of infectious agents and their transmissibility by transfusion.

BACKGROUND: An ongoing issue in transfusion medicine is whether newly identified or emerging pathogens can be transmitted by transfusion. One method to study this question is through the use of a contemporary linked donor-recipient repository. STUDY DESIGN AND METHODS: The Retrovirus Epidemiology Donor Study Allogeneic Donor and Recipient (RADAR) repository was established between 2000 and 2003 by seven blood centers and eight collaborating hospitals. Specimens from consented donors were collected, components from their donations were routed to participating hospitals, and recipients of these units gave enrollment and follow-up specimens for long-term storage. The repository was designed to show that zero transmissions to enrolled recipients would indicate with 95 percent confidence that the transfusion transmission rate of an agent with prevalence of 0.05 to 1 percent was lower than 25 percent. RESULTS: The repository contains pre- and posttransfusion specimens from 3,575 cardiac, vascular, and orthopedic surgery patients, linked to 13,201 donation specimens. The mean number of RADAR donation exposures per recipient is 3.85. The distribution of components transfused is 77 percent red cells, 13 percent whole blood-derived platelet concentrates, and 10 percent fresh frozen plasma. A supplementary unlinked donation repository containing 99,906 specimens from 84,339 donors was also established and can be used to evaluate the prevalence of an agent and validate assay(s) performance before accessing the donor-recipient-linked repository. Recipient testing conducted during the establishment of RADAR revealed no transmissions of human immunodeficiency virus, hepatitis C virus, or human T-lymphotropic virus. CONCLUSIONS: RADAR is a contemporary donor-recipient repository that can be accessed to study the transfusion transmissibility of emerging agents.

Detection of West Nile virus RNA and antibody in frozen plasma components from a voluntary market withdrawal during the 2002 peak epidemic.

BACKGROUND: The US West Nile virus (WNV) epidemic in the summer and fall of 2002 included the first documented cases of transfusion-transmitted WNV infection. In December 2002, the FDA supported a voluntary market withdrawal by the blood banking community of frozen blood components collected in WNV high-activity areas. At the time, the prevalence of viremia and serologic markers for WNV in the blood supply was undefined. STUDY DESIGN AND METHODS: In collaboration with America's Blood Centers, 1468 frozen plasma components (of approx. 60,000 frozen units voluntarily withdrawn from the market) were selectively retrieved from the peak epidemic regions and season (June 23, 2002-September 28, 2002). These units were unlinked, subaliquoted, and tested by WNV enzyme immunoassays (EIAs; Focus Technologies and Abbott Laboratories) and nucleic acid amplification tests (NATs; Gen-Probe Inc. and Roche Molecular Systems). RESULTS: Of the 1468 EIA results from Abbott and Focus, 7 were anti-immunoglobulin M (IgM)- and anti-immunoglobulin G (IgG)-reactive by both assays, 8 and 1 were IgM-only-reactive, and 8 and 23 were IgG-only-reactive, respectively. NAT by Gen-Probe and Roche Molecular Systems yielded one RNA-positive, antibody-negative unit containing approximately 440 RNA copies per mL. An additional 10-fold replicate NAT testing by Gen-Probe on 14 of 15 IgM-reactive specimens yielded 2 additional IgM- and IgG-reactive units with low-level viremia (i.e., 7/10 and 2/10 replicates tested reactive). CONCLUSION: The prevalence of acute (RNA-positive) and recent (IgM-seroreactive) WNV infections indicates that transfusion risk in high-risk areas could have been considerable and that voluntary market withdrawal of frozen components likely averted some WNV transfusion transmissions. The existence of very-low-level viremic units raises concerns, because WNV minipool NAT screening will miss such units and individual NAT may not completely correct this situation.

Folate and cancer: a review of the literature.

Folate, a water-soluble vitamin, part of the vitamin B complex, plays an important role in methylation reactions and DNA/RNA synthesis. This review examines the experimental and epidemiological evidence for the association between folate status and risk of cancer. Data have accumulated indicating that low folate status may promote carcinogenesis. Low folate levels are associated with cytogenetic abnormalities in vivo and in vitro. Findings from animal studies are conflicting and suggest that the effect of folate on neoplasia depends on factors such as the animal and tumor model, the type, timing, dose, and length of application of carcinogen, the stage of carcinogenesis, and the level and form of folate administered. Epidemiological studies examined the association between folate and cancer of the cervix, colorectum, lung, esophagus, and brain and suggest that low folate status may play an important role early in the neoplastic process. The potential for inhibition of precursor lesions in the cervix and colorectum, namely, cervical intraepithelial neoplasia and adenomatous polyps, respectively, is of particular interest. Additional research designed to clarify the role of folate in carcinogenesis is warranted.

Potential increased risk of virus transmission due to exclusion of older donors because of concern over Creutzfeldt-Jakob disease. The National Heart, Lung, and Blood Institute Retrovirus Epidemiology Donor Study.

BACKGROUND: Concern over the theoretical possibility of disease transmission via blood from donors who develop Creutzfeldt-Jakob disease has led to proposals to exclude older individuals from donating plasma for further manufacture into pooled plasma donations. The impact of extending this age-deferral policy to blood donors was examined with respect to the risk for known transmissible viruses. STUDY DESIGN AND METHODS: Demographic characteristics and confirmed prevalence rates (/10(5) first-time donations) and incidence rates (/10(5) person-years for repeat donors) for viral markers were compared for donors < 50 years old (n = 1,259,805 [85%]) and > or = 50 years old (n = 219,856 [15%]) and for donors < 60 years old (n = 1,409,176 [95%]) and > or = 60 years old (n = 70,485 [5%]). Incidence rates were combined with infectious window-period estimates for each virus, to calculate the risk of virus transmission per 10(6) donations. RESULTS: Unadjusted prevalence rates were significantly greater for younger than for older donor groups for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), and hepatitis C virus (HCV) (p < or = 0.05). Incidence rates (and transmission risk estimates) for HBsAg were significantly higher in the < 50 donor group than in the > or = 50 group (p < or = 0.05), and those for HIV, human T-lymphotropic virus, and HCV were not significantly higher (p > 0.05). Blanket removal of donors over the age of 50 would potentially lead to the following significant increases in the risk of infected units: HIV, 12 percent; HCV, 21 percent; and hepatitis B virus (HBsAg), 22 percent. CONCLUSION: Removal of donors over the age of 60 would not significantly affect the risk of infected units. Deferral of donors > or = 50 years of age from whole-blood donations for unfounded concerns about Creutzfeldt-Jakob disease could have adverse effects on both blood availability and safety.

A new superinvasive in vitro phenotype induced by selection of human breast carcinoma cells with the chemotherapeutic drugs paclitaxel and doxorubicin.

Doxorubicin- and paclitaxel-selected variants of an in vitro invasive clonal population of the human breast cancer cell line, MDA-MB-435S, were established by pulse selection, and exhibited a novel 'superinvasive' phenotype. This phenotype is characterised by an ability to relocate to another surface following invasion through matrigel and membrane pores, by decreased adhesion to extracellular matrix proteins and by increased motility. This may represent an in vitro model of a step in the metastatic process occurring subsequent to invasion. The paclitaxel-resistant variants, MDA-MB-435S-F/Taxol-10p and MDA-MB-435S-F/Taxol-10p4p were resistant to paclitaxel, vincristine and docetaxel, but not to doxorubicin, carboplatin, etoposide or 5-fluorouracil. The doxorubicin-selected variants MDA-MB-435S-F/Adr-10p and MDA-MB-435S-F/Adr-10p10p, in contrast, exhibited only small increases in resistance to doxorubicin, although they were slightly resistant to VP-16 and docetaxel, and exhibited increased sensitivity to paclitaxel, carboplatin and 5-fluorouracil.

Incidence rates of viral infections among repeat donors:are frequent donors safer?

BACKGROUND: Incidence rates (IRs) for viral infections may vary with the frequency of donation among repeat, community, whole-blood (WB) donors, with IRs thought to be lower among donors with higher frequency of donation. STUDY DESIGN AND METHODS: IRs for HIV, HTLV, HCV, and HBV infection were stratified by frequency of donation among 868,403 repeat WB donors who gave approximately 4 million donations at five United States blood centers from 1991 through 96. All donors had given at least 2 donations during those years, with the first donation being nonreactive on confirmatory testing. Frequency of donation was measured in three ways: by the number of donations per year; at the time of donation, by the number of donations given within the preceding 2-year period; and by the number of donations given from 1991 through 1993. RESULTS: The IRs for HIV, HCV, and HBV infection did not appear to differ among donors with lower or higher numbers of donation per year. However, the IR for HTLV infection decreased as the number of donations per year increased (p = 0.0004). IRs for all viral markers remained stable, regardless of the number of donations given within the 2-year period before the donation. Although IRs for HIV, HTLV, and HCV infection did not vary by the number of donations given in 1991 through 1993, the IR for HBV infection appeared to be lower in donors who gave more donations in that period (p = 0.01). CONCLUSION: These findings do not provide evidence of a lower IR for transfusion-transmissible viral infections among repeat WB donors who give more frequently. Abbreviated screening histories for frequent repeat donors might not be advisable.

First-time blood donors: demographic trends.

BACKGROUND: With changing demographics of the United States population and the continuous need to recruit new donors, it is important to monitor the demographic profile of first-time donors and to evaluate changes in the donor pool to improve recruitment targeting. STUDY DESIGN AND METHODS: First-time whole blood (n = 901,862) donors at five United States blood centers between 1991 and 1996 were analyzed. RESULTS: The total number of first-time donors appears to be decreasing. Over the 6-year period, there was an overall increase in the proportion of Hispanic and other minority first-time donors and a concurrent decrease in the proportion of white donors at Retrovirus Epidemiology Donor Study centers. Other variables, including age, sex, and education, did not show a consistent trend. CONCLUSION: The demographic profile of first-time donors is changing. These data highlight the importance for blood centers to continuously monitor the donor population. A better understanding of the donor population may help blood centers adjust their donor outreach, recruitment, and retention programs. New recruitment efforts appear needed to counter general apathy toward donating blood, and minority groups appear to be receptive to becoming blood donors.

Knowledge of HIV/AIDS transmission and screening in United States blood donors.

BACKGROUND: Increased knowledge of HIV transmission and behavioral and test screening may encourage high-risk blood donors to self-defer. STUDY DESIGN AND METHODS: Knowledge of HIV transmission and screening and the association with demographics, screening test reactivity, and unreported deferrable risks (UDRs) was assessed by a 1998 anonymous mail survey sent to 92,581 blood donors, of whom 57 percent responded. Groups were compared by using weighted chi-square tests and logistic regression analysis. RESULTS: Four percent of the donors thought that it was very likely or somewhat likely for a person to contract HIV from donating blood, and 20 percent perceived a similar risk from blood transfusion. Only 60 percent of the donors knew that the available screening tests may not detect a recent infection. Thirty-seven percent either did not know or felt it was acceptable to donate blood to obtain HIV testing. Those most likely to answer knowledge questions incorrectly were more likely to have a higher prevalence of test reactivity or UDRs and to be

Repeat whole-blood and plateletpheresis donors:unreported deferrable risks, reactive screening tests, andresponse to incentive programs.

BACKGROUND: Evaluating plateletpheresis (PPH) and repeat community whole-blood (RWB) donors' responses to donation incentive programs is essential for developing effective donor retention programs. STUDY DESIGN AND METHODS: Using data from a 1998 anonymous questionnaire sent to 92,581 US blood donors, the prevalence of unreported deferrable risks, screening test reactivity, and response to incentives were compared in RWB and PPH donors by the use of weighted chi-square tests and logistic regression analyses. RESULTS: From 52,650 respondents, 38,884 RWB and 2,028 PPH donors were identified. Levels of screening test reactivity (1%) and unreported deferrable risks (UDRs, 2-3%) were similar in RWB and PPH donors. RWB and PPH donors were strongly encouraged or discouraged by similar incentives. Of the incentives that would encourage a higher proportion of UDR-free RWB donors to return, cholesterol screening and earning a blood credit appealed to >50 percent. Similar results were obtained for cholesterol screening in PPH donors. Community service or education credits, premarital screening, and cash had limited appeal for PPH and RWB donors, respectively, and would be more likely to differentially encourage donors with a UDR to return. CONCLUSION: Incentives that were associated with the greatest donor appeal and that minimized the potential recruitment of more risky donors were identified.

Prevalence, donation practices, and risk assessment of blood donors with hemochromatosis.

CONTEXT: Despite changes in eligibility policies, practical barriers limit blood donations from individuals with hemochromatosis. Increased knowledge of hemochromatosis donor characteristics may help foster further changes that will promote more donations. OBJECTIVES: To estimate the prevalence of donors diagnosed as having hemochromatosis and to compare rates of unreported deferrable risks for transfusion-transmissible viral infections (TTVIs), positive screening test results for TTVIs, and donation patterns between hemochromatosis patient donors and donors reporting no medical conditions necessitating phlebotomy (non-health-related donors). DESIGN: An anonymous mail survey conducted in 1998 as part of the ongoing Retrovirus Epidemiology Donor Study. SETTING AND PARTICIPANTS: Among a stratified probability sample of 92 581 blood donors from 8 geographically diverse US blood centers, 52 650 (57%) responded. MAIN OUTCOME MEASURES: Prevalence of hemochromatosis among blood donors; prevalence of unreported deferrable risks and positive screening test results for TTVIs among hemochromatosis patient donors vs non-health-related donors. RESULTS: One hundred ninety-seven respondents (0.4%) identified themselves as hemochromatosis patients and 50 079 (95.1%) as non-health-related donors. An estimated 0.8% of all donations were from hemochromatosis patients, 45.8% of whom reported that they had donated blood to treat their illness. The proportion of repeat donors was higher in hemochromatosis patients than in non-health-related donors (83.5% vs 76.5%; P =.03). Among repeat donors, 68.7% of hemochromatosis patients reported donating at least 3 times in the past year compared with 49.1% of non-health-related donors (P<.001). The prevalence of unreported deferrable risks for TTVIs was similar in hemochromatosis patients (2.0%) and non-health-related donors(3.1%) as was the overall prevalence of positive screening test results (1.3% of hemochromatosis patients vs 1.6% of non-health-related donors). CONCLUSIONS: Although significant numbers of hemochromatosis patients reported donating blood for therapeutic reasons, our findings suggest that this population does not present a greater risk to blood safety than other donors.

Trends in incidence and prevalence of major transfusion-transmissible viral infections in US blood donors, 1991 to 1996. Retrovirus Epidemiology Donor Study (REDS)

CONTEXT: Evaluating trends in blood donor infectious disease rates is essential for monitoring blood supply safety and donor screening effectiveness. OBJECTIVE: To determine changes over time in blood donor population infection rates of human immunodeficiency virus (HIV), human T-lymphotropic virus (HTLV), hepatitis C virus (HCV), and hepatitis B virus (HBV). DESIGN: Cross-sectional survey data from the National Heart, Lung, and Blood Institute-sponsored Retrovirus Epidemiology Donor Study. SETTING: Five blood centers in different regions of the United States. PARTICIPANTS: A total of 1.9 million volunteer blood donors with 1 or more nonautologous donations from January 1991 to December 1996. MAIN OUTCOME MEASURES: Changes in rates of HIV, HTLV, HCV, and HBV infections were evaluated by comparing yearly prevalence estimates (per 100,000 donations) for first-time allogeneic donors and period-specific incidence rates (IRs) (per 100,000 person-years) for repeat allogeneic donors between 1991 and 1996 (for HCV, from about March 1992 to June 1996). RESULTS: Prevalence of HIV decreased in first-time donors from 0.030% to 0.015% (P=.006) and HCV prevalence decreased from 0.63% to 0.40% (P<.001). Trends were not statistically significant for the proportion of first-time donors with hepatitis B surface antigen (HBsAg) or HTLV. For repeat donors, IRs did not change significantly, indicating a stable but low level of seroconversion. The overall IRs (95% confidence intervals) per 100,000 person-years were 2.92 (2.26-3.70) for HIV, 1.59 (1.12-2.19) for HTLV, 3.25 (2.36-4.36) for HCV, and an estimated 10.43 (7.99-13. 37) for HBV (based on an HBsAg rate of 2.66 [2.04-3.41] with presumed false-positive results considered negative). The HBV IR estimate with presumed false-positive results considered positive (for comparability to previous analyses) was 17.83 (14.60-21.56). CONCLUSION: The decrease in HIV and HCV prevalence rates, combined with the previously documented lower rates of infection in first-time donors compared with the general population, suggests the continued benefit of behavioral risk factor screening. JAMA. 2000;284:229-235

Demographic characteristics, unreported risk behaviors, and the prevalence and incidence of viral infections: a comparison of apheresis and whole-blood donors. The Retrovirus Epidemiology Donor Study.

BACKGROUND: The demographics, deferrable risk behaviors, and the prevalence and incidence of viral infections of apheresis (PH) and whole-blood (WB) donors were compared, to characterize these two populations and to evaluate the relative safety of PH and WB donors in terms of transfusion-transmitted viral infections. STUDY DESIGN AND METHODS: A comparison was made of 36,119 PH donors (> or = 1 PH donation) and 1.38 million WB donors (> or = 1 WB donation) in terms of demographics and the prevalence (/100,000 donors) and incidence (/100,000 person-years) of viral infections, by using data collected at five United States blood collection centers between 1991 and 1994. Deferrable risk behaviors were defined as those risk behaviors that would have resulted in donor deferral, had they been reported. The prevalence of deferrable risk behaviors was estimated by using data collected through an anonymous mail survey. RESULTS: PH donors were older and more likely than repeat (2+ donations) WB donors to be female, white, and United States-born and to have a higher degree of education (p < or = 0.001). The prevalence of any viral infection was 50 percent higher in WB donors than in PH donors (p = 0.04), whereas the incidence of HIV, human T-lymphotropic virus, and hepatitis B surface antigen was nonsignificantly higher in WB donors. The prevalence of deferrable risk behaviors did not differ in the two groups. CONCLUSION: Further studies will be needed to evaluate whether the difference in the prevalence of viral infections observed in this study can be explained by demographic characteristics and patterns of donation frequency.