Reduction in oral corticosteroid use with mometasone furoate dry powder inhaler improves health-related quality of life in patients with severe persistent asthma.

Severe persistent asthma can have a substantial impact on a patient's health-related quality of life (HRQL), both as a result of symptoms and from side effects of treatment. The HRQL impact of two doses (400 and 800 microg twice daily) of mometasone furoate dry powder inhaler (MF DPI) was compared with placebo in patients with severe persistent asthma previously maintained on oral steroids as a component of a previously published randomized, 12-week, double-blind, placebo-controlled, multicenter trial. A 9-month open-label extension (OLE), with all patients treated with MF DPI, followed. Patients 12 years of age or older completed a generic HRQL measure, the Medical Outcomes Trust Short Form-36 (SF-36), and an asthma-specific measure, the Marks Asthma Quality of Life Questionnaire (AQLQ-M), at baseline, at endpoint (last evaluable visit) of the double-blind phase (EODBP), and after the first 3 months of the OLE. Of 132 patients enrolled in the study, 128 provided HRQL data at baseline and at EODBP. Mean SF-36 scores at baseline showed significant HRQL impairment compared with U.S. general population norms. With treatment, the reduction in oral corticosteroid (OCS) requirements of the MF-DPI-treated groups was accompanied by significant (p < 0.05) improvement over placebo in the physical domain of HRQL (SF-36 physical component summary score and the physical function subscale) at EODBP. MF-DPI-treated patients also showed significant improvements at EODBP in each of the four subscales of the AQLQ-M (p<0.05). From EODBP to the OLE 3-month endpoint, patients treated with MF DPI twice daily maintained, or improved, SF-36 scores in most domains. Symptomatic improvement and reduction in OCS use with MF DPI were accompanied by significant improvement in HRQL in patients with severe persistent asthma. These improvements were maintained during the 3-month period of the OLE in which HRQL was evaluated.     

Preventing child abuse: An experimental evaluation of the child parent enrichment project

Perinatal child abuse prevention projects are increasingly favored but rarely evaluated. The paper describes an experimental evaluation of the Child Parent Enrichment Project (CPEP). Women were referred to the project during or just after pregnancy if identified as at-risk of engaging in child abuse by community professionals. Clients were randomly assigned to CPEP services (n=24) or traditional community services (n=26). CPEP services involved six months of home visiting by paraprofessional women and linkage to other formal and informal community resources. Multivariate Analysis of Covariance on posttest scores, controlling for pretest scores, show advantage for the CPEP group in prenatal care, birth outcomes, better reports of child temperament, and better indicators of child welfare. CPEP mothers tended to report better well-being. No significant differences were demonstrated for levels of formal and informal support. Reports of child abuse were similar for both groups. Consumer satisfaction indicates that clients valued the program. The preliminary results argue for further use and evaluation of perinatal child abuse prevention services.The authors thank Sharon Ikami and CPEP staff and volunteers. Richard P. Barth, D.S.W. is Associated Professor at the School of Social Welfare, University of California, Berkeley. Susan Hacking, Ph.D. was Project Director and Jordana Ash, M.S.W. is Child Welfare Worker, Alameda County Department of Social Services. Funding was provided by Bio-Medical Research Support Grant 2-507-RR07006 Resources from the Division of Research National Institute of Health, the State of California Office of Child Abuse Prevention, and the Office of Human Development Services ACYF, DHHS (Grant #90-CA-0998).     

Impact of intranasal budesonide on immune inflammatory responses and epithelial remodeling in chronic upper airway inflammation

BACKGROUND: Histologic and immunohistologic features of nasal polyps (NP) are similar to those observed in asthma, thus suggesting a similar immunopathology. OBJECTIVE: The primary objective of this study was to further understand the anti-inflammatory and immunoregulatory effects of locally delivered corticosteroids. To this end, the effect of intranasal budesonide on the expression of specific cytokines, lymphocyte subsets, and epithelial remodeling in this model of airway tissue inflammation were studied. METHODS: We used immunohistochemical techniques to examine nasal mucosae (NM) from healthy individuals and nasal polyp (NP) tissues from patients with nasal polyposis obtained before and after intranasal budesonide treatment. RESULTS: First, the density of CD8(+) cells was markedly increased in NP tissues after intranasal budesonide treatment from 16.1 +/- 8.4 (M +/- SEM) per mm(2) to 39.9 +/- 24.1. Second, the density of cells immunoreactive for IL-4, IL-5, IFN-gamma, IL-12, and TGF-beta in NP was significantly greater than in control NM tissues. The density of IL-4(+) and IL-5(+) cells in NP tissues significantly decreased after budesonide treatment from 40 +/- 12 to 17.8 +/- 8 and from 19.3 +/- 11 to 10.4 +/- 7, respectively. In contrast, the density of IFN-gamma(+) and IL-12(+) cells remained unchanged. In addition, we found that the density of TGF-beta(+) cells significantly increased after intranasal budesonide from 18 +/- 5 to 41 +/- 9. Third, damage to the entire length of the NP epithelium was quantified using a grading system. The epithelium of untreated NP was substantially damaged; remarkable epithelial restitution with no apparent changes in stromal collagen deposition was observed after intranasal budesonide treatment. CONCLUSIONS: These findings demonstrate that intranasal budesonide induced an increase in CD8 population and a selective regulatory effect on tissue cytokine expression. Furthermore, intranasal budesonide promoted epithelial remodeling. We hypothesize that these immunoregulatory and remodeling effects elicited by steroids might be, at least in part, mediated by the induction of TGF-beta.     

An investigation of the disclosure process and support needs of BRCA1 and BRCA2 carriers

Disclosure of the results of a positive genetic mutation to offspring can be challenging. The purpose of this study was to investigate the content and process of disclosure from BRCA1/2 carriers to their offspring. A semi-structured questionnaire focused on the disclosure processes between parent and offspring. Thirty-one/40 mothers with BRCA1/2 mutations completed the cross-sectional survey. Sixteen carriers (51.6%) chose to disclose their results to all of their children, thirteen carriers (41.9%) chose not to disclose their results, and two carriers (6.5%) chose to disclose to some of their children. The age of a child appeared to be the most significant contributing factor in the decision to disclose. The mean age of the offspring who learned of the positive test result was 24.3 years with most carriers advocating the ideal age range for disclosure from 19 to 25 years. There was a discrepancy between actual and potential disclosure topics between those who had disclosed and those who had not disclosed at the time of the survey. Women who disclosed their result tended to do so alone, within a week of learning their own results, equally to male and female offspring and expressed that the relationships between themselves and their children had strengthened since revealing the presence of a genetic mutation in the family. Women who had not disclosed the results of their genetic test to offspring were significantly more interested in receiving additional individual counseling, educational videos, and email newsletters that focus on disclosure of this complex and life altering information compared to those who had already disclosed. Disclosure of BRCA1/2 results is determined primarily by age of offspring, is usually done by women alone, relatively soon after receiving results and appears to enhance the relationships between mothers and offspring. Both disclosed and non-disclosed carriers demonstrated significant interest in a variety of interventions to support the disclosure process.     

Meta-analysis of epigenome-wide association studies of carotid intima-media thickness

Common carotid intima-media thickness (cIMT) is an index of subclinical atherosclerosis that is associated with ischemic stroke and coronary artery disease (CAD). We undertook a cross-sectional epigenome-wide association study (EWAS) of measures of cIMT in 6400 individuals. Mendelian randomization analysis was applied to investigate the potential causal role of DNA methylation in the link between atherosclerotic cardiovascular risk factors and cIMT or clinical cardiovascular disease. The CpG site cg05575921 was associated with cIMT (beta?=??0.0264, p value?=?3.5?×?10^–8) in the discovery panel and was replicated in replication panel (beta?=??0.07, p value?=?0.005). This CpG is located at chr5:81649347 in the intron 3 of the aryl hydrocarbon receptor repressor gene (AHRR). Our results indicate that DNA methylation at cg05575921 might be in the pathway between smoking, cIMT and stroke. Moreover, in a region-based analysis, 34 differentially methylated regions (DMRs) were identified of which a DMR upstream of ALOX12 showed the strongest association with cIMT (p value?=?1.4?×?10^–13). In conclusion, our study suggests that DNA methylation may play a role in the link between cardiovascular risk factors, cIMT and clinical cardiovascular disease.

     

Cytokines and pulmonary fibrosis.

Chronically inflamed and fibrotic tissue of the respiratory tract can be shown to actively express the genes and products of a number of powerful growth and differentiating factors. The initial activation of lung inflammatory cells, including alveolar macrophages, is presumed to result in the release of early acting cytokines such as IL-1 and TNF. Subsequent activation and possible phenotype alteration of the structural cells results in release of other growth factors and accumulation of blood derived inflammatory cells. These cells, once they have entered the tissue and become further activated, may begin to release their own autocrine factors and "feed back" some of the similar signals to the tissue cells in a paracrine manner, further inducing differentiation and phenotype change. These internal tissue cell and cytokine cascades could account for the chronic nature of the inflammation. Therapeutic intervention must therefore take into account the inflammatory component as well as the nature of the cytokines and structural cells involved in the propagation of the disease.     

Service-Learning in Communities of Elders (SLICE): Development and Evaluation of an Introductory Geriatrics Course for Medical Students

Problem: Medical students have limited exposure to Geriatrics in their traditional training. Service-learning offers students the opportunity to engage with older adult communities and become more comfortable interacting with this population. Intervention: A preclinical elective course was developed to expand medical students' experiences in Geriatrics through service-learning. In this course, students conducted needs assessments in diverse older adult communities, created health education projects to address community-identified needs, and reflected on their experiences through written assignments and presentations. The course instructor presented lectures on special topics in Geriatrics, including ageism and health literacy. The curriculum aimed to familiarize students with older adults' needs in a variety of settings. Context: Over 3 years, 74 students participated in the service-learning course. Students were assigned to older adult community sites, where they conducted needs assessments and designed and implemented original educational projects targeting community concerns. Program evaluation methods included a validated survey assessing students' attitudes toward older adults, course evaluations, review of student assignments and projects, and feedback from older adult participants and site coordinators. Outcome: Students gained hands-on experience working with older adults and designing appropriate health education projects. Analysis of attitude surveys demonstrated students' increased interest in Geriatrics as a career. Both students and older adult participants described enjoyable, valuable experiences gained from service-learning activities. Lessons Learned: Students appreciated the combination of community and classroom learning about Geriatrics. Service-learning was most constructive at sites with responsive coordinators, engaged older adults, and a need for health education resources. The course challenged students to assess health needs in communities that included cognitively impaired elders and to design educational projects tailored to older adults.     

Genetic stability of Brucella abortus S19 and RB51 vaccine strains by multiple locus variable number tandem repeat analysis (MLVA16)

The aims of the present study were (i) to assess the in vitro genetic stability of S19 and RB51 Brucella abortus vaccines strains and (ii) to evaluate the ability of multiple-locus variable-number tandem repeat (VNTR) analysis (MLVA) as a tool to be used in the quality control of live vaccines against brucellosis. Sixty-three batches of commercial S19 (n = 53) and RB51 (n = 10) vaccines, produced between 2006 and 2009, were used in this study. S19 and RB51 vaccines were obtained from, respectively, seven and two different manufacturers. Ten in vitro serial passages were performed on reference strains and on selected batches of commercial vaccines. All batches, reference strains and strains of serial passages were typed by the MLVA16. The results demonstrated that B. abortus S19 and RB51 vaccine strains are genetically stable and very homogeneous in their respective groups. Anyway, batches of S19 from one manufacturer and batches of RB51 from another presented genotypes distincts from the reference vaccine strains. In both cases, differences were found on locus Bruce07, which had addition of one repeat unit in the case of S19 batches and the deletion of one repeat unit in the case of RB51 batches. In summary, MLVA16 proved to be a molecular tool capable of discriminating small genomic variations and should be included in in vitro official tests.     

Pathways to recovery: recovery housing models for men who have sex with men (MSM)

Background & Aims: Gay, bisexual, and other men who have sex with men (MSM) face distinct recovery challenges. This mixed-methods study examines the service needs and help-seeking pathways of MSM (N?=?25) living in a group of recovery residences operated in Texas, one of which is a home specifically designated for gay and bisexual men.

Methods: Upon intake, adult MSM were recruited to complete an interview assessing the extent of their service needs as well as their recovery goals and expectations about their stay. Men were recruited regardless of whether they moved into the home designated for gay and bisexual men or into another one of the men’s homes.

Results: MSM in the sample reported high rates of health conditions, depression, victimization, and sex risk behaviors. A greater number of them entering the gay and bisexual men’s home reported being in recovery from amphetamine use, having a chronic medical problem, and being physically assaulted as an adult. The majority of MSM, regardless of home type, were seeking emotional and social support as well as accountability in their recovery home experience, but MSM in the gay and bisexual men’s home talked about emotion and social support most frequently and within the context of emotional safety.

Conclusions: MSM entering recovery housing have complex service needs. Recovery housing may play an important role in supporting recovery among MSM. Residences specifically for them could be tailored to address their unique needs by fostering connections to other sexual minorities in recovery and facilitating social identity transformation.