The purpose of the study was to analyze clinical and/or autopsy findings at the time of death among adults with sickle cell disease (SCD) at Howard University in Washington, DC over a 25-year period. A single physician recorded circumstances of death among 141 adult SCD patients he treated and knew well from 1976 to 2001. These findings were determined by autopsy report and/or clinical assessment. In a subset of 31 patients, autopsy records were reviewed for reports of iron deposition in liver and heart and of organ pathology. One hundred and fourteen (80.9%) of the patients had SS phenotype and 66 (46.8%) were female. The mean ± SD age at death was 36 ± 11 years. Leading circumstances of death included pulmonary hypertension (PHT) (26.2%), sudden death (23.4%), renal failure (22.6%), infection (18.4%), thromboembolism (14.9%), cardiac diagnoses (12.0%), cirrhosis (11.3%), pneumonia or acute chest syndrome (9.9%), bleeding (7.8%), and iron overload (7.0%). When circumstances of deaths that occurred after 1991 (n = 69) were compared to those that occurred in 1991 or earlier (n = 72), PHT (36.2% vs. 16.6%; P < 0.01) was significantly more common in 1992 or later. Significant associations were found between PHT and thromboembolism and between cirrhosis and iron overload. In this proportional mortality study of adults with SCD, PHT was the leading finding at the time of death. Thromboembolism was associated with PHT, and iron overload was associated with cirrhosis. Am. J. Hematol. 81:858-863, 2006. V V C 2006 Wiley-Liss, Inc.

Purpose To identify successful recruitment strategies, challenges and best practices for researchers to engage African American communities in clinical studies taken into consideration target participants’ culture and context. Methods We reviewed 50 studies conducted from 2001-2012 at an inner-city research center to determine the type, duration, anticipated enrollments and actual enrollments. Survey was sent to study coordinators to obtain data on recruitment and retention strategies, challenges and dropout rates. We also interviewed 25 study coordinators on challenges and strategies. Results Of the 50 studies, 24 had completed recruitment at the time of this report. The completed studies achieved a median recruitment rate of 88% [range: 50-110]. Successful recruitment and retention strategies included: field-based strategy and snowballing. Major barriers were: distrust, compensation, education disadvantage, lack of interest and inability to have study partner. Strategies to reduce barriers included providing informational sessions, disseminating newsletters about study outcomes. Best practices include being culturally sensitive including demonstrating a caring attitude and being responsive to participants needs. Conclusions Cultural competence is critical in order to design and implement successful recruitment strategies in this population. Research teams should comprised of multi-ethnic staff, involve the community, demonstrate trust and deliver concise education of the research endeavor.

CYP3A4-V, an A to G promoter variant associated with prostate cancer in African Americans, exhibits large differences in allele frequency between populations. Given that the African American population is genetically heterogeneous because of its African ancestry and subsequent admixture with European Americans, case-control studies with African Americans are highly susceptible to spurious associations. To test for association with prostate cancer, we genotyped CYP3A4-V in 1376 (2 N) chromosomes from prostate cancer patients and age- and ethnicity-matched controls representing African Americans, Nigerians, and European Americans. To detect population stratification among the African American samples, 10 unlinked genetic markers were genotyped. To correct for the stratification, the uncorrected association statistic was divided by the average of association statistics across the 10 unlinked markers. Sharp differences in CYP3A4-V frequencies were observed between Nigerian and European American controls (0.87 and 0.10, respectively; P<0.0001). African Americans were intermediate (0.66). An association uncorrected for stratification was observed between CYP3A4-V and prostate cancer in African Americans (P=0.007). A nominal association was also observed among European Americans (P=0.02) but not Nigerians. In addition, the unlinked genetic marker test provided strong evidence of population stratification among African Americans. Because of the high level of stratification, the corrected P-value was not significant (P=0.25). Follow-up studies on a larger dataset will be needed to confirm whether the association is indeed spurious; however, these results reveal the potential for confounding of association studies by using African Americans and the need for study designs that take into account substructure caused by differences in ancestral proportions between cases and controls.

Context Perceived discriminatory experiences in society have been associated with a higher burden of pain among some minority patient populations. Objectives To describe the extent to which patients with sickle cell disease (SCD) perceive discrimination from health care providers, and to examine the association of these experiences with the burden of chronic SCD pain. Methods Cross-sectional analysis of data collected at baseline of a prospective cohort study of SCD patient experiences of care (n = 291). Perceived race-based and disease-based discrimination from health care providers were measured using subscales adapted from the Interpersonal Processes of Care Survey. Discrimination scores were examined for their association with patient characteristics and measures of pain burden using descriptive, bivariate, and multivariate analytic techniques. Results Respondents reported a greater burden of race-based discrimination from health care providers than has been previously reported by African Americans, and they reported a greater amount of disease-based versus race-based discrimination. While age and having difficulty persuading providers about pain were the only patient characteristics independently associated with race-based discrimination, older age, greater emergency room utilization, having difficulty persuading providers about pain, daily chronic pain, fewer “good days” during a week, and a higher severity of pain on their “good days” were independently associated with greater disease-based discrimination. Conclusion Perceived disease-based, but not race-based, discrimination was found to be associated with a greater range of self-reported pain among patients with SCD. If causal, this finding could signal an important new approach to mitigating the burden of pain experienced by persons with SCD.