Serum microRNA expression patterns that predict early treatment failure in prostate cancer patients

We aimed to identify microRNA (miRNA) expression patterns in the serum of prostate cancer (CaP) patients that predict the risk of early treatment failure following radical prostatectomy (RP). Microarray and Q-RT-PCR analyses identified 43 miRNAs as differentiating disease stages within 14 prostate cell lines and reflectedpublically available patient data. 34 of these miRNA were detectable in the serum of CaP patients. Association with time to biochemical progression was examined in a cohort of CaP patients following RP. A greater than two-fold increase in hazard of biochemical progression associated with altered expression of miR-103, miR-125b and miR-222 (p <.0008) in the serum of CaP patients. Prediction models based on penalized regression analyses showed that the levels of the miRNAs and PSA together were better at detecting false positives than models without miRNAs, for similar level of sensitivity. Analyses of publically available data revealed significant and reciprocal relationships between changes in CpG methylation and miRNA expression patterns suggesting a role for CpG methylation to regulate miRNA. Exploratory validation supported roles for miR-222 and miR-125b to predict progression risk in CaP. The current study established that expression patterns of serum-detectable miRNAs taken at the time of RP are prognostic for men who are at risk of experiencing subsequent early biochemical progression. These non-invasive approaches could be used to augment treatment decisions.     

Public attitudes toward an authorization for contact program for clinical research

We conducted an online experimental survey to evaluate attitudes toward an authorization for contact (AFC) program allowing researchers to contact patients about studies based on electronic record review. A total of 1070 participants were randomly assigned to 1 of 3 flyers varying in design and framing. Participants were asked to select concerns about and reasons for signing up for AFC. Logistic regression and latent class analysis were conducted. The most commonly selected concerns included needing more information (43%), privacy (40%), and needing more time to think (28%). A minority were not interested in participating in research (16%) and did not want to be bothered (15%). Latent class analysis identified clusters with specific concerns about privacy, lack of interest in research, and not wanting to be bothered. A novel flyer with simple and positive framing was associated with lower odds of both not wanting to be bothered (P = .01) and not being interested in research (P = .01). Many concerns about AFC programs appear nonspecific. Addressing privacy, lack of interest in research, and not wanting to be bothered warrant further study as ways to enhance recruitment.     

The Development and Implementation of an Interdisciplinary On-Line Academic Course Using a Life Course Perspective

The University of Wisconsin–Madison Pediatric Pulmonary Center (UW PPC) provides interdisciplinary leadership training for graduate students and postgraduate professionals. The training includes a three-credit on-line course entitled Interdisciplinary Care of Children with Special Health Care Needs. This paper describes the course, the content and organization of which was guided by the life course perspective (LCP). The UW PPC team used the LCP to guide course organization, content development, and evaluation approaches. UW PPC trainees took responsibility for content areas, performed literature reviews and reviews of resources, and suggested student activities. Course content was focused on the child with special health care needs (CSHCN) embedded in contextual environments of family, community, culture, and larger social and public policy arenas. The content included three case-study videos that followed a child with cystic fibrosis from birth to age 18. Key concepts of the LCP were woven in throughout the videos and other course materials. Emphasis was on representing development of the individual during critical/sensitive periods and on social determinants of health. At semester’s end, qualitative and quantitative student evaluation results were very positive for all areas of the course. The final course paper, organized similarly to course modules, synthesized all aspects of the course. A successful paper included LCP concepts woven throughout to show integration of course content. The LCP provided a useful framework for course organization and content, and served as a lens through which students came to understand the care needs of CSHCN and their families. A course such as this can serve the important goal of educating future maternal child health professionals in using the LCP to understand how multiple determinants of health interact across the life span to produce health outcomes in this population.     

Increased Risk of Acute Hepatitis B among Adults with Diagnosed Diabetes MellitusIncreased Risk of Acute Hepatitis B among Adults with Diagnosed Diabetes Mellitus

Introduction

The risk of acute hepatitis B among adults with diabetes mellitus is unknown. We investigated the association between diagnosed diabetes and acute hepatitis B.

Methods

Confirmed acute hepatitis B cases were reported in 2009–2010 to eight Emerging Infections Program (EIP) sites; diagnosed diabetes status was determined. Behavioral Risk Factor Surveillance System respondents residing in EIP sites comprised the comparison group. Odds ratios (ORs) comparing acute hepatitis B among adults with diagnosed diabetes versus without diagnosed diabetes were determined by multivariate logistic regression, adjusting for age, sex, and race/ethnicity, and stratified by the presence or absence of risk behaviors for hepatitis B virus (HBV) infection.

Results

During 2009–2010, EIP sites reported 865 eligible acute hepatitis B cases among persons aged ≥23 years; 95 (11.0%) had diagnosed diabetes. Comparison group diabetes prevalence was 9.1%. Among adults without hepatitis B risk behaviors and with reported diabetes status, the OR for acute hepatitis B comparing adults with and without diabetes was 1.9 (95% confidence interval [CI] = 1.4, 2.6); ORs for adults ages 23–59 and ≥60 years were 2.1 (95% CI = 1.6, 2.8) and 1.5 (95% = CI 0.9, 2.5), respectively.

Conclusions

Diabetes was independently associated with an increased risk for acute hepatitis B among adults without HBV risk behaviors.     

Adherence with bisphosphonate therapy in US veterans with rheumatoid arthritis

Objective

Pharmacy Benefits Management program data for patients enrolled in the Veterans Affairs Rheumatoid Arthritis (VARA) registry were linked with clinical data to determine bisphosphonate adherence and persistence among US veterans with rheumatoid arthritis (RA) and to determine factors associated with adherence.

Methods

The primary outcome measures were the duration of bisphosphonate therapy and the medication possession ratio (MPR). Patients with an MPR <0.80 were classified as nonadherent. Potential covariates considered in the analysis included patient demographics, RA disease activity and severity parameters, and factors associated with osteoporosis risk. Associations of patient factors with duration of therapy and adherence were examined using multivariable regression modeling.

Results

Bisphosphonates were prescribed to 573 (41.5%) of 1,382 VARA subjects. The mean ± SD duration of therapy for bisphosphonates was 39.2 ± 31.4 months. A longer duration of therapy correlated with older age, more years of education, and dual x‐ray absorptiometry testing. The mean ± SD MPR of VARA subjects for bisphosphonate therapy was 0.69 ± 0.28; 302 (52.7%) were nonadherent. In multivariate analyses, nonadherence with bisphosphonate therapy was associated with a longer duration of RA disease (odds ratio [OR] 1.02, 95% confidence interval [95% CI] 1.00–1.04) and duration of bisphosphonate therapy >32 months (OR 1.63, 95% CI 1.04–2.57). Whites were less likely to have a low MPR compared with nonwhites (OR 0.52, 95% CI 0.30–0.88).

Conclusion

Nonadherence with bisphosphonates was common in this cohort of RA patients and was associated with nonwhite ethnicity, a longer duration of RA disease, and a greater duration of bisphosphonate therapy.     

PEPFAR's support for orphans and vulnerable children: some beneficial effects, but too little data, and programs spread thin

Sixteen million children in developing and middle-income countries have been orphaned by HIV/AIDS, and at least another million children per year are rendered vulnerable by parental HIV/AIDS-related illness. Since 2003 the US government has provided approximately $1.6 billion to give four million of these children care and support through the President's Emergency Plan for AIDS Relief (PEPFAR). We conducted five studies to evaluate the effectiveness of PEPFAR's interventions for such children in East Africa and southern Africa. We found evidence of beneficial changes in school enrollment rates and on the psychosocial well-being of children. However, we could not demonstrate empirically the impact of most of the PEPFAR initiatives that we examined, primarily because of a lack of baseline data and clear outcome and impact indicators. We also found that many programs were spread so thin across a vulnerable population that little in the way of services actually reached beneficiaries, which raises questions about whether PEPFAR funds are sufficient, or if the program is attempting to do much with too few resources. We offer several recommendations, including better measuring the effect of programs for orphans and vulnerable children by collecting baseline data and conducting well-designed, rigorous outcome and impact evaluations.