Evidence of fibrinogen as a target of citrullination in IgM rheumatoid factor-positive polyarticular juvenile idiopathic arthritis

<p>Abstract</p> <p>Background</p> <p>Several studies have noted the significance of measuring anti-cyclic citrullinated peptide (CCP) antibodies in juvenile idiopathic arthritis (JIA) as an important indicator for destructive disease, as is the case in rheumatoid arthritis (RA). While the role of anti-CCP antibodies in RA and JIA has become better understood, the identity of the target proteins of this modification has remained elusive. In this study, we evaluated serum from patients with various subtypes of JIA to investigate the presence of anti-deiminated (citrullinated) fibrinogen and anti-citrullinated α-enolase antibodies, and their association with RF and anti-CCP antibody isotypes.</p> <p>Methods</p> <p>Sera were obtained from 96 JIA patients, 19 systemic lupus erythematosus (SLE) patients, and 10 healthy children. All sera were measured for antibodies against citrullinated and native fibrinogen and α-enolase by an enzyme linked immunosorbent assay (ELISA). In addition, all sera were assayed for anti-CCP antibody isotypes and rheumatoid factor (RF) isotypes by ELISA. The relationship between anti-citrullinated fibrinogen and anti-α-enolase antibodies and disease activity and joint damage were also investigated. All results were correlated with clinical and laboratory parameters using Spearman's rho correlation coefficient. Multiple logistic regression analysis was utilized to identify which variables were associated with joint erosions and diagnosis of JIA.</p> <p>Results</p> <p>Thirty-one JIA patients (32%) demonstrated reactivity to citrullinated fibrinogen and 9 (9%) to citrullinated α-enolase. Reactivity to citrullinated fibrinogen and α-enolase was predominantly found in IgM RF-positive polyarthritis patients. Fourteen JIA patients reacted with native α-enolase and a higher percentage of SLE patients reacted with citrullinated α-enolase when compared to JIA patients. Anti-citrullinated fibrinogen antibodies correlated with the presence of IgG anti-CCP antibodies and IgA and IgM RF. The presence of anti-citrullinated α-enolase antibodies correlated with IgA anti-CCP antibodies. IgG anti-CCP antibodies were significantly associated with joint damage and anti-citrullinated fibrinogen antibodies were strongly associated with JIA when compared to control groups. Anti-citrullinated fibrinogen antibodies demonstrated high sensitivity (81%) for IgM RF-positive polyarticular JIA. IgG anti-CCP antibodies had the highest specificity (95%) for JIA, with anti-citrullinated fibrinogen antibodies, IgA anti-CCP antibodies and IgA RF all following at 84%.</p> <p>Conclusions</p> <p>JIA patient sera exhibited strong reactivity to anti-citrullinated fibrinogen antibodies and demonstrated high sensitivity and specificity for JIA, primarily in IgM RF-positive polyarthritis patients. Fibrinogen is one of several protein targets for citrullination in JIA.</p

ENGAGING CLINICIANS IN A PRE-IMPLEMENTATION ASSESSMENT OF THE WOMEN & PERSON-EMPOWERED COMMUNITY ACCESS FOR REPRODUCTIVE EQUITY (WE CARE) INTERVENTION

Objectives: To assess clinicians’ perspectives on WE CARE (an emergency department (ED) family planning counseling and referral intervention that uses an online health tool and community health workers) to inform intervention design for implementation. Methods: We conducted one-on-one, semi-structured interviews with Emergency Medicine, Family Medicine, and Obstetrics & Gynecology clinicians until thematic saturation. The Consolidated Framework for Implementation Research (CFIR) informed the interview guide and was used to code all transcripts. A CFIR expert conducted an external coding audit. Results: We interviewed 30 clinicians (female (77%), ED staff (47%), white (63%), and attending physicians (43%)). WE CARE was highly acceptable. Dominant CFIR domains include: (1) Clinicians suggested Design Quality and Packaging modifications, particularly the referral processes, to promote successful implementation; (2) transportation and insurance were essential Patient Needs and Resources; (3) WE CARE was Compatible with the Value of “no missed opportunity” to help patients; (4) Compatibility with Work Processes – WE CARE posed scheduling and reimbursement challenges to clinics; (5) Clinicians expressed concerns about an ED Culture of reproductive health frustrations, resistance to change, and competing priorities. Others identified the ED “safety net” culture and long wait times as assets to the intervention; (6) WE CARE had a significant Relative Advantage over the status quo. A few clinicians identified more advantageous alternatives (e.g., WE CARE in the clinic, home, or community settings); (7) Engaging Key Stakeholders throughout the hospital was a critical implementation element. Conclusions: Clinicians contextualized several implementation constructs relevant to designing and implementing an ED family planning intervention

Knowledge and Beliefs about Mechanism of Action of Birth Control Methods among European Women

Background: Adequate knowledge is essential for making informed decisions. We attempted to determine the level of knowledge about mechanisms of action of birth control methods in five representative samples of European women. Study design: Randomly selected women, aged 18-49 years, completed an anonymous survey in Germany, France, the UK, Sweden and Romania (N=1137). Participants were asked about how contraceptive methods work and if providers should inform them about this issue. Multiple linear regression was used to evaluate women’s characteristics associated with their knowledge of mechanisms of action. Results: The majority of women identified the unequivocal mode of action of condoms, sterilization and abortion. Less than 2% identified all possible mechanisms of action of hormonal contraceptives and intrauterine devices. Highly-educated women correctly identified the mechanism or mechanisms of action of more methods than less educated women (β coef.=0.22, 95%CI=0.01-0.43). Regardless of their sociodemographic characteristics and their belief about when human life begins, most women (75%) stated that the provider should inform them about possible postfertilization effects. Conclusions: European women have low knowledge about mechanisms of action of several contraceptive methods. The majority want to be informed about possible postfertilization effects. Since adequate knowledge is essential for making informed decisions, providers are encouraged to inform women about all possible mechanisms of action of contraceptives

Quality of Care in Contraceptive Services Provided to Young People in Two Ugandan Districts: A Simulated Client Study

BACKGROUND: Low and inconsistent use of contraceptives by young people contributes to unintended pregnancies. This study assessed quality of contraceptive services for young people aged 15-24 in two rural districts in Uganda. METHODS: Five female and two male simulated clients (SCs) interacted with 128 providers at public, private not-for-profit (PNFP), and private for profit (PFP) health facilities. After consultations, SCs were interviewed using a structured questionnaire. Six aspects of quality of care (client's needs, choice of contraceptive methods, information given to users, client-provider interpersonal relations, constellation of services, and continuity mechanisms) were assessed. Descriptive statistics and factor analysis were performed. RESULTS: Means and categorized quality scores for all aspects of quality were low in both public and private facilities. The lowest quality scores were observed in PFP, and medium scores in PNFP facilities. The choice of contraceptive methods and interpersonal relations quality scores were slightly higher in public facilities. Needs assessment scores were highest in PNFP facilities. All facilities were classified as having low scores for appropriate constellation of services. Information given to users was suboptimal and providers promoted specific contraceptive methods. Minority of providers offered preferred method of choice and showed respect for privacy. CONCLUSIONS: The quality of contraceptive services provided to young people was low. Concurrent quality improvements and strengthening of health systems are needed

Sociocultural Determinants of Teenage Childbearing Among Latinas in California

Objectives U.S. Latinas have a persistently high rate of teenage childbearing, which is associated with adverse outcomes for both mother and child. This study was designed to investigate the roles of socioeconomic factors and acculturation in teenage childbearing in this population. Methods Logistic regression was used to analyze the association of measures of acculturation (language spoken at home, nativity, and age at immigration) and respondents’ parents’ education with age at first birth in a stratified sample of post-partum women in California. Results The unadjusted odds ratio for teenage birth for Latinas versus non-Latina Whites was 5.2 (95% CI 4.1–6.6). Nativity was not significantly associated with teen birth, but speaking Spanish at home was positively associated and immigrating at a later age was negatively associated with teen birth. Overall, these measures of acculturation accounted for 17% (95% CI 8–28%) of the difference in odds of teen birth between Latinas and non-Latina Whites. Higher levels of education among respondents’ parents had differentially protective effects across the racial/ethnic groups. Controlling for disparities in respondents’ parents’ education without changing its differential effects across racial/ethnic groups reduced the odds ratio for Latinas compared to non-Latina Whites by 30% (95% CI 14–60%). Conclusion These findings call into question common assumptions about the protective effect of acculturation on teen fertility and suggest that improving childhood socioeconomic factors among Latinas may decrease teen childbearing

The professionalism disconnect: Do entering residents identify yet participate in unprofessional behaviors?

Background Professionalism has been an important tenet of medical education, yet defining it is a challenge. Perceptions of professional behavior may vary by individual, medical specialty, demographic group and institution. Understanding these differences should help institutions better clarify professionalism expectations and provide standards with which to evaluate resident behavior. Methods Duke University Hospital and Vidant Medical Center/East Carolina University surveyed entering PGY1 residents. Residents were queried on two issues: their perception of the professionalism of 46 specific behaviors related to training and patient care; and their own participation in those specified behaviors. The study reports data analyses for gender and institution based upon survey results in 2009 and 2010. The study received approval by the Institutional Review Boards of both institutions. Results 76% (375) of 495 PGY1 residents surveyed in 2009 and 2010 responded. A majority of responders rated all 46 specified behaviors as unprofessional, and a majority had either observed or participated in each behavior. For all 46 behaviors, a greater percentage of women rated the behaviors as unprofessional. Men were more likely than women to have participated in behaviors. There were several significant differences in both the perceptions of specified behaviors and in self-reported observation of and/or involvement in those behaviors between institutions. Respondents indicated the most important professionalism issues relevant to medical practice include: respect for colleagues/patients, relationships with pharmaceutical companies, balancing home/work life, and admitting mistakes. They reported that professionalism can best be assessed by peers, patients, observation of non-medical work and timeliness/detail of paperwork. Conclusion Defining professionalism in measurable terms is a challenge yet critical in order for it to be taught and assessed. Recognition of the differences by gender and institution should allow for tailored teaching and assessment of professionalism so that it is most meaningful. A shared understanding of what constitutes professional behavior is an important first step