Improving diversity in study participation: Patient perspectives on barriers,racial differences and the role of communities

IntroductionThe lack of racial/ethnic diversity in research potentially limits the generalizability of findings to a broader population, highlighting the need for greater diversity and inclusion in clinical research. Qualitative research (i.e., focus groups) was conducted to identify (i) the potential motivators and barriers to study participation across different races and ethnicities; (ii) preferred delivery of education and information to support healthcare decision‐making and the role of the community.MethodsPatient focus groups were conducted with 26 participants from the sponsor''s Patient Engagement Research Councils selected through subjective sampling. Recruitment prioritized adequate representation across different race/ethnic groups. Participation was voluntary and participants underwent a confidential interview process before selection. Narrative analysis was used to identify themes and draw insights from interactions. Experienced research specialists identified emerging concepts, and these were tested against new observations. The frequency of each concept was examined to understand its importance.ResultsBased on self‐selected race/ethnicity, participants were divided into five focus groups (Groups: African American/Black: 2; Hispanic/Latino, Asian American, and white: 1 each) and were asked to share their experiences/opinions regarding the stated objectives. Barriers to study participation included: limited awareness of opportunities to participate in research, fears about changes in standard therapy, breaking cultural norms/stigma, religion‐related concerns and mistrust of clinical research. Participants identified the importance of transparency by pharmaceutical companies and other entities to build trust and partnership and cited key roles that communities can play. The perceptions of the African American group regarding diversity/inclusion in research studies appeared to be different from other groups; a lack of trust in healthcare providers, concerns about historical instances of research abuse and the importance of prayer were cited.ConclusionThis study provided insights into barriers to study participation, and also highlighted the need for pharmaceutical companies and other entities to authentically engage in strategies that build trust within communities to enhance recruitment among diverse populations.Patient or Public ContributionThe data collected in the present study was provided by the participants in the focus groups.     

Expression of a cloned denV gene of bacteriophage T4 in Escherichia coli.

A 713-base-pair Hae III fragment from bacteriophage T4 encompassing the denV gene with its preceding promoter has been cloned in a pBR322-derived positive-selection vector and introduced into a variety of DNA repair-deficient uvr and rec and uvr,rec Escherichia coli strains. The denV gene was found to be expressed, probably from its own promoter, causing pyrimidine dimer incision-deficient uvrA, uvrB, uvrC strains to be rescued by the denV gene. A uvrD (DNA helicase II) strain was also complemented, but to a lesser extent. A wild-type strain did not seem to be affected at the UV doses tested. Surprisingly, all recA, recB, and recC strains tested also showed an increased UV resistance, perhaps by reinforcement of the intact uvr system in these strains. Complementation of denV- T4 strains and host-cell reactivation of lambda phage was also observed in denV+ E. coli strains. Equilibrium sedimentation showed that DNA repair synthesis occurred in a UV-irradiated uvrA E. coli strain carrying the cloned denV gene. Southern blotting confirmed our earlier results [Valerie, K., Henderson, E. E. & de Riel, J. K. (1984) Nucleic Acids Res. 12, 8085-8096] that the denV gene is located at 64 kilobases on the T4 map. Phage T2 (denV-) did not hybridize to a denV-specific probe.     

Genetic complementation of UV-induced DNA repair in Chinese hamster ovary cells by the denV gene of phage T4.

The denV gene of phage T4, encoding the pyrimidine dimer-specific DNA repair enzyme endonuclease V, has been introduced by DNA transfection into the UV-sensitive DNA repair-deficient Chinese hamster ovary (CHO) cell line UV5. Transformants were first selected for resistance to the antibiotic G418 conferred by the neo gene from Tn5 carried by the same plasmid. A majority of the isolated G418-resistant UV5 clones also showed an increased resistance to 254-nm UV light. One clone, designated I-A1, was found to have an intermediate level of colony-forming ability after UV irradiation when compared to UV5 and wild-type AA8 cells. A Southern blot showed that I-A1 carries a single integrated intact copy of the denV gene. Alkaline sucrose gradients revealed a dose-dependent appearance of breaks in the DNA of I-A1 cells following UV-irradiation, while unirradiated cells did not exhibit any significant breaks. Analysis of DNA repair by isopycnic sedimentation showed that DNA excision repair by I-A1 was at least equal to the level of repair in AA8 cells. These results show that the prokaryotic denV gene can restore UV repair capabilities in vivo to CHO UV5 cells defective in repair of UV-induced damage.     

Age-related changes in cardiac muscarinic receptors: decreased ability of the receptor to form a high affinity agonist binding state

Cardiac ventricular muscarinic cholinergic receptors and agonist binding properties were determined in Fischer 344 rats at 3, 12, and 24 months of age. Muscarinic receptors were determined by specific (-)-[3H]quinuclidinyl benzilate (QNB) binding, and the agonist binding properties were determined by competition assays. There were no differences in the concentration of the receptor or the dissociation constant of [3H]QNB binding among the three age groups. In cardiac membranes from 3- and 12-month-old animals, 5'-guanylyl-imidodiphosphate (Gpp(NH)p) increased by 16- to 18-fold (p less than .01) the concentration of carbachol required to inhibit [3H]QNB binding by 50% (IC50). At 24 months, however, Gpp(NH)p induced only a 2.7-fold shift in the carbachol IC50 value (p less than .01). The reduced shift was due to an increase in the carbachol IC50 value determined in the absence of Gpp(NH)p (p less than .01). There was no significant differences among the 3-, 12-, and 24-month-old animals in the half-maximal concentration of Gpp(NH)p required to produce the carbachol IC50 shift. The data indicated that with age there is a reduced ability of the muscarinic receptor to form a high affinity agonist binding state.     

Comparison of the treadmill exercise score and single-photon emission computed tomographic thallium imaging in risk assessment

Background  

This study compared the prognostic value of exercise single-photon emission computed tomographic (SPECT) thallium imaging with that of treadmill exercise score in medically treated patients with coronary artery disease (CAD)     

Structural valve deterioration in mitral replacement surgery: comparison of Carpentier-Edwards supra-annular porcine and perimount pericardial bioprostheses.

BACKGROUND: Bioprostheses preserved with glutaraldehyde, both porcine and pericardial, have been available as second-generation prostheses for valve replacement surgery. The performance with regard to structural valve deterioration with the Carpentier-Edwards supra-annular (CE-SAV) porcine bioprosthesis and the Carpentier-Edwards Perimount (CE-P) pericardial bioprosthesis (Baxter Healthcare Corp, Edwards Division, Santa Ana, Calif) was evaluated to determine whether there was a difference in mitral valve replacement. METHODS: The CE-SAV bioprosthesis was implanted in 1266 overall mitral valve replacements (isolated mitral, 1066; mitral in multiple, 200) and the CE-P bioprosthesis in 429 overall mitral valve replacements (isolated mitral, 328; mitral in multiple, 101). The mean age of the CE-SAV population was 64.2 +/- 12.2 years and that of the CE-P population, 60.7 +/- 11.7 years (P =.0001). For the study, structural valve deterioration was diagnosed at reoperation for explantation. RESULTS: The freedom from structural valve deterioration was evaluated to 10 years, and the freedom rates reported are at 10 years. For the overall mitral valve replacement groups, the actuarial freedom from deterioration was significant (P =.0001): CE-P > CE-SAV for 40 years or younger, 80% versus 60%; 41 to 50 years, 91% versus 61%; 51 to 60 years, 84% versus 69%; 61 to 70 years, 95% versus 75%. The older than 70-year group was 100% versus 92% (no significant difference). The actual freedom from structural valve deterioration also demonstrated the same pattern at 10 years: 40 years or younger, CE-P 82% versus CE-SAV 68%; 41 to 50 years, 92% versus 70%; 51 to 60 years, 90% versus 80%; 61 to 70 years, 97% versus 88%; and older than 70 years, 100% versus 97%. The independent risk factors of structural valve deterioration for the overall mitral valve replacement group were age and age groups and prosthesis type (CE-SAV > CE-P). The prosthesis type either in isolated replacement or in multiple replacement was not predictive of structural valve deterioration. The pathology of structural valve deterioration was different: 70% of CE-P failures were due to calcification and 57% of CE-SAV failures were due to combined calcification and leaflet tear. CONCLUSION: The actuarial and actual freedom from structural valve deterioration, diagnosed at reoperation, is greater at 10 years for CE-P than for CE-SAV bioprostheses. The mode of failure is different, and the cause remains obscure. Long-term evaluation is recommended, because the different modes of failure may alter the clinical performance by 15 and 20 years.     

Insulin-Like Growth Factor I Is a Determinant of Hip Bone Mineral Density in Men Less Than 60 years of Age: MINOS Study

Several studies show that in elderly men bone mineral density (BMD) is not correlated with the insulin-like growth factor (IGF-I) level, but data are scanty in young men. Results of studies correlating insulin-like growth factor binding protein 3 (IGFBP-3) and BMD in men are discordant. As different hypotheses can explain the discordant results, we evaluated the correlation of BMD with serum IGF-I, IGFBP-3, and IGF-I/IGFBP-3 index in a large cohort of 721 men aged 19–85 years taking into account age, body weight, 17-estradiol, free testosterone, and parathyroid hormone. Serum IGF-I and IGFBP-3 decreased with age (r = –0.44 and r = –0.36, P = 0.0001). After adjustment for confounding variables, IGF-I correlated weakly positively with BMD and with bone mineral apparent density (BMAD) of hip as well as with cortical thickness of femoral neck, both of which are determined mainly by bone resorption, but not with bone size determined by periosteal apposition. IGF-I correlated weakly positively with BMD at the whole body and at the third lumbar vertebra IGFBP-3 and IGF-I/IGFBP-3 index did not correlate with densitometric parameters. In men aged 19–60 years, IGF-I correlated with BMD and BMAD of total hip and with cortical thickness of femoral neck positively and more strongly than in the entire cohort but not with the size of proximal femur. BMD of total hip was 6% higher in men in the highest quartile of IGF-I than in men in the lowest quartile. IGF-I, IGFBP-3, and IGF-I/IGFBP-3 index did not correlate with densitometric parameters of other sites. In the men aged more than 60 years, neither IGF-I nor IGFBP-3 nor IGF-I/IGFBP-3 index correlated with BMD, BMAD, or bone size. In men aged 19–60 years, the most significant hormonal determinants of BMD and BMAD of the hip and of the cortical thickness of femoral neck were 17-estradiol and IGF-I (P < 0.05–0.0001). In men aged more than 60 years, the most significant determinants of hip BMD were 17-estradiol and PTH. In conclusion, IGF-I seems to contribute to the inhibition of bone resorption and to maintaining bone mass of the proximal femur during the phase of slow bone loss in men aged less than 60 years. IGFBP-3 and IGF-I/IGFBP-3 index were not correlated with BMD or bone size. Supported by a contract with INSERM/Merck Sharp & Dohme Chibret, Paris, France