Long-term health-related quality of life and walking capacity of lung recipients with and without bronchiolitis obliterans syndrome

BACKGROUND: Outcome after lung transplantation (LTx) is affected by the onset of bronchiolitis obliterans syndrome (BOS) and lung function decline. Reduced health-related quality of life (HRQL) and physical mobility have been shown in patients developing BOS, but the impact on the capacity to walk is unknown. We aimed to compare the long-term HRQL and 6-minute walk test (6MWT) between lung recipients affected or not by BOS Grade > or =2. METHODS: Fifty-eight patients were prospectively followed for 5.6 +/- 2.9 years after LTx. Assessments included the St George's Respiratory Questionnaire (SGRQ) and the 6MWT, which were performed yearly. Moreover, clinical complications were recorded to estimate the proportion of the follow-up time lived without clinical intercurrences after transplant. Analyses were performed using adjusted linear regression and repeated-measures analysis of variance. RESULTS: BOS was a significant predictor of lower SGRQ scores (p < 0.01) and reduced time free of clinical complications (p = 0.001), but not of 6MWT distance (p = 0.12). At 7 years post-transplant, results were: 69.0 +/- 21.8% vs 86.9 +/- 5.6%, p < 0.05 (SGRQ); 58.5 +/- 21.6% vs 88.7 +/- 11.4%, p < 0.01 (proportion of time lived without clinical complications); and 82.2 +/- 10.9% vs 91.9 +/- 14.2%, p = 0.27 (percent of predicted 6MWT), respectively, for patients with BOS and without BOS. CONCLUSIONS: Despite significantly less time lived without clinical complications and progressive decline of self-reported health status, the capacity to walk of patients affected by BOS remained relatively stable over time. These findings may indicate that the development of moderate to severe BOS does not prevent lung recipients from walking independently and pursuing an autonomous life.

Individual patient data meta-analysis of diagnostic and prognostic studies in obstetrics, gynaecology and reproductive medicine

BACKGROUND: In clinical practice a diagnosis is based on a combination of clinical history, physical examination and additional diagnostic tests. At present, studies on diagnostic research often report the accuracy of tests without taking into account the information already known from history and examination. Due to this lack of information, together with variations in design and quality of studies, conventional meta-analyses based on these studies will not show the accuracy of the tests in real practice. By using individual patient data (IPD) to perform meta-analyses, the accuracy of tests can be assessed in relation to other patient characteristics and allows the development or evaluation of diagnostic algorithms for individual patients. In this study we will examine these potential benefits in four clinical diagnostic problems in the field of gynaecology, obstetrics and reproductive medicine. METHODS/DESIGN: Based on earlier systematic reviews for each of the four clinical problems, studies are considered for inclusion. The first authors of the included studies will be invited to participate and share their original data. After assessment of validity and completeness the acquired datasets are merged. Based on these data, a series of analyses will be performed, including a systematic comparison of the results of the IPD meta-analysis with those of a conventional meta-analysis, development of multivariable models for clinical history alone and for the combination of history, physical examination and relevant diagnostic tests and development of clinical prediction rules for the individual patients. These will be made accessible for clinicians. DISCUSSION: The use of IPD meta-analysis will allow evaluating accuracy of diagnostic tests in relation to other relevant information. Ultimately, this could increase the efficiency of the diagnostic work-up, e.g. by reducing the need for invasive tests and/or improving the accuracy of the diagnostic workup. This study will assess whether these benefits of IPD meta-analysis over conventional meta-analysis can be exploited and will provide a framework for future IPD meta-analyses in diagnostic and prognostic research.

When one depends on the other: reporting of interaction in case-control and cohort studies

BACKGROUND: Interaction refers to the situation in which the effect of 1 exposure on an outcome differs across strata of another exposure. We did a survey of epidemiologic studies published in leading journals to examine how interaction is assessed and reported. METHODS: We selected 150 case-control and 75 cohort studies published between May 2001 and May 2007 in leading general medicine, epidemiology, and clinical specialist journals. Two reviewers independently extracted data on study characteristics. RESULTS: Of the 225 studies, 138 (61%) addressed interaction. Among these, 25 (18%) presented no data or only a P value or a statement of statistical significance; 40 (29%) presented stratum-specific effect estimates but no meaningful comparison of these estimates; and 58 (42%) presented stratum-specific estimates and appropriate tests for interaction. Fifteen articles (11%) presented the individual effects of both exposures and also their joint effect or a product term, providing sufficient information to interpret interaction on an additive and multiplicative scale. Reporting was poorest in articles published in clinical specialist articles and most adequate in articles published in general medicine journals, with epidemiology journals in an intermediate position. CONCLUSIONS: A majority of articles reporting cohort and case-control studies address possible interactions between exposures. However, in about half of these, the information provided was unsatisfactory, and only 1 in 10 studies reported data that allowed readers to interpret interaction effects on an additive and multiplicative scale.

Neighborhood Violence and Adolescent Friendships

This paper investigates the social consequences of neighborhood violence. Using ego-centered friendship network data from the National Longitudinal Study of Adolescent Health, a survey of adolescents in the United States in the mid-1990s, it examines the relationship between neighborhood violence and the quantity, closeness, and composition of adolescent same sex friendships. Though neighborhood violence is unrelated to quantity and closeness net of individual and family characteristics, it predicts boys’ friendships with individuals who no longer attend school (who are presumably older or have dropped out of school) and predicts boys’ and girls’ friendships with individuals who attend other schools. These results are consistent with the theory that violence and fear of victimization focus adolescents’ social attention on their neighborhoods and lead them to develop friendships with individuals who can help them to stay safe. By structuring who adolescents interact with, neighborhood violence may play a role in determining the cultural messages and ideals to which they are exposed.

European veterinary public health specialization: post-graduate training and expectations of potential employers

Residents of the European College of Veterinary Public Health (ECVPH) carried out a survey to explore the expectations and needs of potential employers of ECVPH diplomates and to assess the extent to which the ECVPH post-graduate training program meets those requirements. An online questionnaire was sent to 707 individuals working for universities, government organizations, and private companies active in the field of public health in 16 countries. Details on the structure and activities of the participants' organizations, their current knowledge of the ECVPH, and potential interest in employing veterinary public health (VPH) experts or hosting internships were collected. Participants were requested to rate 22 relevant competencies according to their importance for VPH professionals exiting the ECVPH training. A total of 138 completed questionnaires were included in the analysis. While generic skills such as "problem solving" and "broad horizon and inter-/multidisciplinary thinking" were consistently given high grades by all participants, the importance ascribed to more specialized skills was less homogeneous. The current ECVPH training more closely complies with the profile sought in academia, which may partly explain the lower employment rate of residents and diplomates within government and industry sectors. The study revealed a lack of awareness of the ECVPH among public health institutions and demonstrated the need for greater promotion of this veterinary specialization within Europe, both in terms of its training capacity and the professional skill-set of its diplomates. This study provides input for a critical revision of the ECVPH curriculum and the design of post-graduate training programs in VPH.

Poverty, Educational Attainment and Health Among America’s Children: Current and Future Effects of Population Diversification and Associated Socioeconomic Change

A complex of interrelated factors including minority status, poverty, education, health status, and other factors determine the general welfare of children in America, particularly in heavily diverse states such as Texas. Although racial/ethnic status is clearly only a concomitant factor in that determination it is a factor for which future projections are available and for which the relationships with the other factors in the complex can be assessed. After examining the nature of the interrelationships between these factors we utilize direct standardization techniques to examine how the future diversification of the United States and Texas will affect the number of children in poverty, the educational status of the householders in households in which children in poverty live and the health status of children in 2040 assuming that the current relationships between minority status and these socioeconomic factors continue into the future. In the results of the analyses, data are compared with the total population of the United States and Texas in 2040 assumed in the first simulation scenario, to have the race/ethnicity characteristics of 2008 and in the second those projected for 2040 by the U.S. Census Bureau for the nation and by the Texas State Data Center for Texas in 2040. The results show that the diversification of the population could increase the number of children in poverty in the United States by nearly 1.8 million more than would occur with the lower levels of diversification evident in 2008. In addition, poverty would become increasingly concentrated among minority children with minority children accounting for 76.2 percent of all children in poverty by 2040 and with Hispanic children accounting for nearly half of the children in poverty by 2040. Results for educational attainment show an increasing concentration of minority children in households with householders with very low levels of education such that by 2040, 85.2 percent of the increase in the number of children in poverty would be in households with a householder with less than a high school level of education. Finally, the results related to several health status factors show that children in poverty will have a higher prevalence of nearly all health conditions. For example, the number of children with untreated dental conditions could increase to more than 4 million in the United States and to nearly 500,000 in Texas. The results clearly show that improving the welfare of children in America will require concerted efforts to change the poverty, educational, and health status characteristics associated with minority status and particularly Hispanic status. Failing to do so will lead to a future in which America’s children are increasingly impoverished, more poorly educated, and less healthy and which, as a result, is an America with a more tentative future.

Constitutive NF-kappaB and NFAT activation leads to stimulation of the BLyS survival pathway in aggressive B-cell lymphomas.

B-lymphocyte stimulator (BLyS), a relatively recently recognized member of the tumor necrosis factor ligand family (TNF), is a potent cell-survival factor expressed in many hematopoietic cells. BLyS binds to 3 TNF-R receptors, TACI, BCMA, BAFF-R, to regulate B-cell survival, differentiation, and proliferation. The mechanisms involved in BLYS gene expression and regulation are still incompletely understood. In this study, we examined BLYS gene expression, function, and regulation in B-cell non-Hodgkin lymphoma (NHL-B) cells. Our studies indicate that BLyS is constitutively expressed in aggressive NHL-B cells, including large B-cell lymphoma (LBCL) and mantle cell lymphoma (MCL), playing an important role in the survival and proliferation of malignant B cells. We found that 2 important transcription factors, NF-kappaB and NFAT, are involved in regulating BLyS expression through at least one NF-kappaB and 2 NFAT binding sites in the BLYS promoter. We also provide evidence suggesting that the constitutive activation of NF-kappaB and BLyS in NHL-B cells forms a positive feedback loop associated with lymphoma cell survival and proliferation. Our findings indicate that constitutive NF-kappaB and NFAT activations are crucial transcriptional regulators of the BLyS survival pathway in malignant B cells that could be therapeutic targets in aggressive NHL-B.

Analysis of clonality and antibiotic resistance among early clinical isolates of Enterococcus faecium in the United States.

BACKGROUND: The Enterococcus faecium genogroup, referred to as clonal complex 17 (CC17), seems to possess multiple determinants that increase its ability to survive and cause disease in nosocomial environments. METHODS: Using 53 clinical and geographically diverse US E. faecium isolates dating from 1971 to 1994, we determined the multilocus sequence type; the presence of 16 putative virulence genes (hyl(Efm), esp(Efm), and fms genes); resistance to ampicillin (AMP) and vancomycin (VAN); and high-level resistance to gentamicin and streptomycin. RESULTS: Overall, 16 different sequence types (STs), mostly CC17 isolates, were identified in 9 different regions of the United States. The earliest CC17 isolates were part of an outbreak that occurred in 1982 in Richmond, Virginia. The characteristics of CC17 isolates included increases in resistance to AMP, the presence of hyl(Efm) and esp(Efm), emergence of resistance to VAN, and the presence of at least 13 of 14 fms genes. Eight of 41 of the early isolates with resistance to AMP, however, were not in CC17. CONCLUSIONS: Although not all early US AMP isolates were clonally related, E. faecium CC17 isolates have been circulating in the United States since at least 1982 and appear to have progressively acquired additional virulence and antibiotic resistance determinants, perhaps explaining the recent success of this species in the hospital environment.