Exploring differential item functioning in the SF-36 by demographic, clinical, psychological and social factors in an osteoarthritis population

The SF-36 is a very commonly used generic measure of health outcome in osteoarthritis (OA). An important, but frequently overlooked, aspect of validating health outcome measures is to establish if items work in the same way across subgroup of a population. That is, if respondents have the same 'true' level of outcome, does the item give the same score in different subgroups or is it biased towards one subgroup or another. Differential item functioning (DIF) can identify items that may be biased for one group or another and has been applied to measuring patient reported outcomes. Items may show DIF for different conditions and between cultures, however the SF-36 has not been specifically examined in an osteoarthritis population nor in a UK population. Hence, the aim of the study was to apply the DIF method to the SF-36 for a UK OA population. The sample comprised a community sample of 763 people with OA who participated in the Somerset and Avon Survey of Health. The SF-36 was explored for DIF with respect to demographic, social, clinical and psychological factors. Well developed ordinal regression models were used to identify DIF items. Results: DIF items were found by age (6 items), employment status (6 items), social class (2 items), mood (2 items), hip v knee (2 items), social deprivation (1 item) and body mass index (1 item). Although the impact of the DIF items rarely had a significant effect on the conclusions of group comparisons, in most cases there was a significant change in effect size. Overall, the SF-36 performed well with only a small number of DIF items identified, a reassuring finding in view of the frequent use of the SF-36 in OA. Nevertheless, where DIF items were identified it would be advisable to analyse data taking account of DIF items, especially when age effects are the focus of interest

Network model of immune responses reveals key effectors to single and co-infection dynamics by a respiratory bacterium and a gastrointestinal helminth

Co-infections alter the host immune response but how the systemic and local processes at the site of infection interact is still unclear. The majority of studies on co-infections concentrate on one of the infecting species, an immune function or group of cells and often focus on the initial phase of the infection. Here, we used a combination of experiments and mathematical modelling to investigate the network of immune responses against single and co-infections with the respiratory bacterium Bordetella bronchiseptica and the gastrointestinal helminth Trichostrongylus retortaeformis. Our goal was to identify representative mediators and functions that could capture the essence of the host immune response as a whole, and to assess how their relative contribution dynamically changed over time and between single and co-infected individuals. Network-based discrete dynamic models of single infections were built using current knowledge of bacterial and helminth immunology; the two single infection models were combined into a co-infection model that was then verified by our empirical findings. Simulations showed that a T helper cell mediated antibody and neutrophil response led to phagocytosis and clearance of B. bronchiseptica from the lungs. This was consistent in single and co-infection with no significant delay induced by the helminth. In contrast, T. retortaeformis intensity decreased faster when co-infected with the bacterium. Simulations suggested that the robust recruitment of neutrophils in the co-infection, added to the activation of IgG and eosinophil driven reduction of larvae, which also played an important role in single infection, contributed to this fast clearance. Perturbation analysis of the models, through the knockout of individual nodes (immune cells), identified the cells critical to parasite persistence and clearance both in single and co-infections. Our integrated approach captured the within-host immuno-dynamics of bacteria-helminth infection and identified key components that can be crucial for explaining individual variability between single and co-infections in natural populations

Exploring differential item functioning in the Western Ontario and McMaster Universities osteoarthritis index (WOMAC)

Background: The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) is a widely used patient reported outcome in osteoarthritis. An important, but frequently overlooked, aspect of validating health outcome measures is to establish if items exhibit differential item functioning (DIF). That is, if respondents have the same underlying level of an attribute, does the item give the same score in different subgroups or is it biased towards one subgroup or another. The aim of the study was to explore DIF in the Likert format WOMAC for the first time in a UK osteoarthritis population with respect to demographic, social, clinical and psychological factors. Methods: The sample comprised a community sample of 763 people with osteoarthritis who participated in the Somerset and Avon Survey of Health. The WOMAC was explored for DIF by gender, age, social deprivation, social class, employment status, distress, body mass index and clinical factors. Ordinal regression models were used to identify DIF items. Results: After adjusting for age, two items were identified for the physical functioning subscale as having DIF with age identified as the DIF factor for 2 items, gender for 1 item and body mass index for 1 item. For the WOMAC pain subscale, for people with hip osteoarthritis one item was identified with age-related DIF. The impact of the DIF items rarely had a significant effect on the conclusions of group comparisons. Conclusions: Overall, the WOMAC performed well with only a small number of DIF items identified. However, as DIF items were identified in for the WOMAC physical functioning subscale it would be advisable to analyse data taking into account the possible impact of the DIF items when weight, gender or especially age effects, are the focus of interest in UK-based osteoarthritis studies. Similarly for the WOMAC pain subscale in people with hip osteoarthritis it would be worthwhile to analyse data taking into account the possible impact of the DIF item when age comparisons are of primary interest

Role of Acetyl-Phosphate in Activation of the Rrp2-RpoN-RpoS Pathway in Borrelia burgdorferi

Borrelia burgdorferi, the Lyme disease spirochete, dramatically alters its transcriptome and proteome as it cycles between the arthropod vector and mammalian host. During this enzootic cycle, a novel regulatory network, the Rrp2-RpoN-RpoS pathway (also known as the σ54–σS sigma factor cascade), plays a central role in modulating the differential expression of more than 10% of all B. burgdorferi genes, including the major virulence genes ospA and ospC. However, the mechanism(s) by which the upstream activator and response regulator Rrp2 is activated remains unclear. Here, we show that none of the histidine kinases present in the B. burgdorferi genome are required for the activation of Rrp2. Instead, we present biochemical and genetic evidence that supports the hypothesis that activation of the Rrp2-RpoN-RpoS pathway occurs via the small, high-energy, phosphoryl-donor acetyl phosphate (acetyl∼P), the intermediate of the Ack-Pta (acetate kinase-phosphate acetyltransferase) pathway that converts acetate to acetyl-CoA. Supplementation of the growth medium with acetate induced activation of the Rrp2-RpoN-RpoS pathway in a dose-dependent manner. Conversely, the overexpression of Pta virtually abolished acetate-induced activation of this pathway, suggesting that acetate works through acetyl∼P. Overexpression of Pta also greatly inhibited temperature and cell density-induced activation of RpoS and OspC, suggesting that these environmental cues affect the Rrp2-RpoN-RpoS pathway by influencing acetyl∼P. Finally, overexpression of Pta partially reduced infectivity of B. burgdorferi in mice. Taken together, these findings suggest that acetyl∼P is one of the key activating molecule for the activation of the Rrp2-RpoN-RpoS pathway and support the emerging concept that acetyl∼P can serve as a global signal in bacterial pathogenesis

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

No Association of Xenotropic Murine Leukemia Virus-Related Viruses with Prostate Cancer

BACKGROUND: The association of the xenotropic murine leukemia virus-related virus (XMRV) with prostate cancer continues to receive heightened attention as studies report discrepant XMRV prevalences ranging from zero up to 23%. It is unclear if differences in the diagnostic testing, disease severity, geography, or other factors account for the discordant results. We report here the prevalence of XMRV in a population with well-defined prostate cancers and RNase L polymorphism. We used broadly reactive PCR and Western blot (WB) assays to detect infection with XMRV and related murine leukemia viruses (MLV). METHODOLOGY/PRINCIPAL FINDINGS: We studied specimens from 162 US patients diagnosed with prostate cancer with a intermediate to advanced stage (Gleason Scores of 5-10; moderate (46%) poorly differentiated tumors (54%)). Prostate tissue DNA was tested by PCR assays that detect XMRV and MLV variants. To exclude contamination with mouse DNA, we also designed and used a mouse-specific DNA PCR test. Detailed phylogenetic analysis was used to infer evolutionary relationships. RNase L typing showed that 9.3% were homozygous (QQ) for the R462Q RNase L mutation, while 45.6% and 45.1% were homozygous or heterozygous, respectively. Serologic testing was performed by a WB test. Three of 162 (1.9%) prostate tissue DNA were PCR-positive for XMRV and had undetectable mouse DNA. None was homozygous for the QQ mutation. Plasma from all three persons was negative for viral RNA by RT-PCR. All 162 patients were WB negative. Phylogenetic analysis inferred a distinct XMRV. CONCLUSIONS AND THEIR SIGNIFICANCE: We found a very low prevalence of XMRV in prostate cancer patients. Infection was confirmed by phylogenetic analysis and absence of contaminating mouse DNA. The finding of undetectable antibodies and viremia in all three patients may reflect latent infection. Our results do not support an association of XMRV or MLV variants with prostate cancer

An intervention program with the aim to improve and maintain work productivity for workers with rheumatoid arthritis: design of a randomized controlled trial and cost-effectiveness study

<p>Abstract</p> <p>Background</p> <p>Workers with rheumatoid arthritis (RA) often experience restrictions in functioning at work and participation in employment. Strategies to maintain work productivity exist, but these interventions do not involve the actual workplace. Therefore the aim of this study is to investigate the (cost)effectiveness of an intervention program at the workplace on work productivity for workers with RA.</p> <p>Methods/design</p> <p>This study is a randomized controlled trial (RCT) in specialized rheumatology treatment centers in or near Amsterdam, the Netherlands. Randomisation to either the control or the intervention group is performed at patient level. Both groups will receive care as usual by the rheumatologist, and patients in the intervention group will also take part in the intervention program. The intervention program consists of two components; integrated care, including a participatory workplace intervention. Integrated care involves a clinical occupational physician, who will act as care manager, to coordinate the care. The care manager has an intermediate role between clinical and occupational care. The participatory workplace intervention will be guided by an occupational therapist, and involves problem solving by the patient and the patients’ supervisor. The aim of the workplace intervention is to achieve consensus between patient and supervisor concerning feasible solutions for the obstacles for functioning at work. Data collection will take place at baseline and after 6 and 12 months by means of a questionnaire. The primary outcome measure is work productivity, measured by hours lost from work due to presenteeism. Secondary outcome measures include sick leave, quality of life, pain and fatigue. Cost-effectiveness of the intervention program will be evaluated from the societal perspective.</p> <p>Discussion</p> <p>Usual care of primary and outpatient health services is not aimed at improving work productivity. Therefore it is desirable to develop interventions aimed at improving functioning at work. If the intervention program will be (cost)effective, substantial improvements in work productivity might be obtained among workers with RA at lower costs. Results are expected in 2015.</p> <p>Trial registration number</p> <p>NTR2886</p

Development of cognitive enhancers based on inhibition of insulin-regulated aminopeptidase

The peptides angiotensin IV and LVV-hemorphin 7 were found to enhance memory in a number of memory tasks and reverse the performance deficits in animals with experimentally induced memory loss. These peptides bound specifically to the enzyme insulin-regulated aminopeptidase (IRAP), which is proposed to be the site in the brain that mediates the memory effects of these peptides. However, the mechanism of action is still unknown but may involve inhibition of the aminopeptidase activity of IRAP, since both angiotensin IV and LVV-hemorphin 7 are competitive inhibitors of the enzyme. IRAP also has another functional domain that is thought to regulate the trafficking of the insulin-responsive glucose transporter GLUT4, thereby influencing glucose uptake into cells. Although the exact mechanism by which the peptides enhance memory is yet to be elucidated, IRAP still represents a promising target for the development of a new class of cognitive enhancing agents

Depression and HIV in Botswana: A Population-Based Study on Gender-Specific Socioeconomic and Behavioral Correlates

Depression is a leading contributor to the burden of disease worldwide, a critical barrier to HIV prevention and a common serious HIV co-morbidity. However, depression screening and treatment are limited in sub-Saharan Africa, and there are few population-level studies examining the prevalence and gender-specific factors associated with depression.We conducted a cross-sectional population-based study of 18–49 year-old adults from five districts in Botswana with the highest prevalence of HIV-infection. We examined the prevalence of depressive symptoms, using a Hopkins Symptom Checklist for Depression (HSCL-D) score of ≥1.75 to define depression, and correlates of depression using multivariate logistic regression stratified by sex.Of 1,268 participants surveyed, 25.3% of women and 31.4% of men had depression. Among women, lower education (adjusted odds ratio [AOR] 2.07, 95% confidence interval [1.30–3.32]), higher income (1.77 [1.09–2.86]), and lack of control in sexual decision-making (2.35 [1.46–3.81]) were positively associated with depression. Among men, being single (1.95 [1.02–3.74]), living in a rural area (1.63 [1.02–2.65]), having frequent visits to a health provider (3.29 [1.88–5.74]), anticipated HIV stigma (fearing discrimination if HIV status was revealed) (2.04 [1.27–3.29]), and intergenerational sex (2.28 [1.17–4.41]) were independently associated with depression.Depression is highly prevalent in Botswana, and its correlates are gender-specific. Our findings suggest multiple targets for screening and prevention of depression and highlight the need to integrate mental health counseling and treatment into primary health care to decrease morbidity and improve HIV management efforts