[Clinical significance of determination of DFS70 antibodies to rule out connective tissue diseases]. / Klinische Wertigkeit der Bestimmung von DFS70-Antikörpern für den Ausschluss von Kollagenosen.

BACKGROUND: Connective tissue diseases (CTD) are autoimmune diseases highly associated with the presence of antinuclear antibodies (ANA). Since ANA and musculoskeletal symptoms are not uncommon in the general population, differential diagnostic challenges frequently occur for the treating physician. Dense fine speckled antibodies (DFS70) were recently discovered but their presence appeared to be rare in CTD. METHODS: In this cross-sectional study a total of 270 patients treated in the Rheumatism Center of the Ruhr Area (Rheumazentrum Ruhrgebiet) were preferentially included, when they were ANA+ (≥1:80). Other autoantibodies and DFS70 antibodies were also investigated. The diagnosis of CTD was confirmed by rheumatologists. The sensitivity, specificity and the positive predictive value of DFS70 antibodies were differentially evaluated for various ANA titers. RESULTS: In 91 (33.7%) of the ANA+ patients (33.7%) the diagnosis of CTD was confirmed and in 84 (92.3%) the ANA titer was ≥1:160. The DFS70 antibodies were detected in 17 out of 130 ANA+ patients without CTD (13.1%) versus 2 ANA+ patients (2.2%) with CTD (p = 0.027). None of the patients with ANA 1:80 had DFS70 antibodies. The specificity of DFS70 antibodies to detect the absence of CTD was 97.6%, the sensitivity was 13.1% and the positive predictive value was 89.5%. There was almost no effect of the strength of the different ANA titers. CONCLUSION: It was found that DFS70 antibodies are rarely present in ANA+ patients with CTD but the diagnosis of CTD cannot be reliably ruled out solely by the presence of DFS70 antibodies; however, the high specificity of DFS70 antibodies can be of clinical importance in unclear situations and in cases of anxious patients.

The balance of adult mental health care: provision of core health versus other types of care in eight European countries.

AIMS: Although many mental health care systems provide care interventions that are not related to direct health care, little is known about the interfaces between the latter and core health care. 'Core health care' refers to services whose explicit aim is direct clinical treatment which is usually provided by health professionals, i.e., physicians, nurses, psychologists. 'Other care' is typically provided by other staff and includes accommodation, training, promotion of independence, employment support and social skills. In such a definition, 'other care' does not necessarily mean being funded or governed differently. The aims of the study were: (1) using a standard classification system (Description and Evaluation of Services and Directories in Europe for Long Term Care, DESDE-LTC) to identify 'core health' and 'other care' services provided to adults with mental health problems; and (2) to investigate the balance of care by analysing the types and characteristics of core health and other care services. METHODS: The study was conducted in eight selected local areas in eight European countries with different mental health systems. All publicly funded mental health services, regardless of the funding agency, for people over 18 years old were identified and coded. The availability, capacity and the workforce of the local mental health services were described using their functional main activity or 'Main Types of Care' (MTC) as the standard for international comparison, following the DESDE-LTC system. RESULTS: In these European study areas, 822 MTCs were identified as providing core health care and 448 provided other types of care. Even though one-third of mental health services in the selected study areas provided interventions that were coded as 'other care', significant variation was found in the typology and characteristics of these services across the eight study areas. CONCLUSIONS: The functional distinction between core health and other care overcomes the traditional division between 'health' and 'social' sectors based on governance and funding. The overall balance between core health and other care services varied significantly across the European sites. Mental health systems cannot be understood or planned without taking into account the availability and capacity of all services specifically available for this target population, including those outside the health sector.

Mucosal mast cells are indispensable for the timely termination of Strongyloides ratti infection.

Mast cells and basophils are innate immune cells with overlapping functions that contribute to anti-helminth immunity. Mast cell function during helminth infection was previously studied using mast cell-deficient Kit-mutant mice that display additional mast cell-unrelated immune deficiencies. Here, we use mice that lack basophils or mucosal and connective tissue mast cells in a Kit-independent manner to re-evaluate the impact of each cell type during helminth infection. Neither mast cells nor basophils participated in the immune response to tissue-migrating Strongyloides ratti third-stage larvae, but both cell types contributed to the early expulsion of parasitic adults from the intestine. The termination of S. ratti infection required the presence of mucosal mast cells: Cpa3Cre mice, which lack mucosal and connective tissue mast cells, remained infected for more than 150 days. Mcpt5Cre R-DTA mice, which lack connective tissue mast cells only, and basophil-deficient Mcpt8Cre mice terminated the infection after 1 month with wild-type kinetics despite their initial increase in intestinal parasite burden. Because Cpa3Cre mice showed intact Th2 polarization and efficiently developed protective immunity after vaccination, we hypothesize that mucosal mast cells are non-redundant terminal effector cells in the intestinal epithelium that execute anti-helminth immunity but do not orchestrate it.

European Union investment and countries' involvement in mental health research between 2007 and 2013.

OBJECTIVES: This study aimed to estimate the commitment to mental health research by the European Union (EU) through the 7th framework (FP7) and the competitiveness and innovation (CIP) programmes during the 2007-2013 period. METHODS: Research projects dedicated or partially related to mental health were identified using keywords in the CORDIS database that inventories all FP7 and CIP research projects. We then contacted projects' principal investigators to access the budget breakdown by country and performed an imputation of the distribution of funding between countries based on projects' and participants' characteristics where information was missing. RESULTS: Among the 25 783 research projects funded by the FP7 and the CIP, 215 (0.8%) were specifically dedicated to mental health and 170 (0.7%) were partially related to mental health. They received €607.1 million representing 1.4% of FP7 total funding. Within the FP7-Health subprogramme, the projects represented 5.2% of funding. Important variations appeared across EU countries both for raw funding, which varied between €0 and €77M, and for funding per 100 inhabitants, which varied between €0 and €293. CONCLUSION: EU funding of mental health research does not match the burden incurred by mental disorders and must be increased in the next framework programme.

Fragile X syndrome: economic burden and health-related quality of life of patients and caregivers in France.

BACKGROUND: Fragile X syndrome (FXS) is the main hereditary cause of intellectual disability. Although the associated burden appears to be considerable, to date no study has comprehensively assessed the cost incurred because of FXS, including its specific impact on health-related quality of life and the burden on caregivers using standardised quantitative tools. The aim of this article is to provide data in order to increase awareness of the repercussions of FXS on patients and caregivers as well as on the health and social care systems in France. METHODS: A retrospective cross-sectional study was carried out on 145 patients recruited through Le Goëland X-Fragile and Mosaïques, the French FXS patient associations. Data on their demographic characteristics and resource use were obtained from an online questionnaire, and costs were estimated by a bottom-up approach. The EQ-5D health questionnaire was used to measure patients' and caregivers' health-related quality of life. Perceived burden of care was measured using the Zarit Caregiver Burden Interview. The Barthel index, a non-utility-based assessment, was used to measure patients' level of dependence. RESULTS: The annual total direct cost of FXS was estimated at €25 800 per patient. The main contributors were informal care provided by the main caregiver (€10 500) and social services (€8400). Healthcare costs, estimated at €2700, represented only a minor share. Mean EQ-5D utility scores were 0.49 for patients and 0.75 for caregivers. The mean burden for caregivers as measured by the Zarit Caregiver Burden Interview was 39.9. CONCLUSIONS: Fragile X syndrome requires significant resources that are mainly of a non-medical nature and are higher for children than for adults. Compared with related diseases, it constitutes a particularly high burden for caregivers. Using a bottom-up approach and a wide range of standardised measures, this study underscores the need for greater awareness of the burden of FXS as well as an assessment of new and existing interventions to address it.

Real-life evidence in evaluating effectiveness of treatment in Haemophilia A with a recombinant FVIII concentrate: a non-interventional study in emerging countries.

Some progress has been made regarding availability of recombinant factor VIII concentrates and prophylaxis for haemophilia A in emerging countries, where plasma-derived concentrates were used in the vast majority. Clinical studies to document their introduction and effectiveness are so far not widely available in literature. This non-interventional study evaluates the real-life effectiveness and safety of prophylactic and on-demand treatment with recombinant factor VIII formulated with sucrose (rFVIII-FS) for bleed control and preservation of joints in emerging countries from Eastern Europe, North Africa and Middle East area. One hundred and eighty-six patients from 11 countries were enrolled, mean ± SD age 12.8 ± 12.7 years. At enrolment, majority (79.6%) had severe haemophilia A (<2% IU mL(-1) ), 47.8% had a target joint, 15% had an inhibitor history and one patient was on immune tolerance induction. During the 24-month observation period, 58.1% of the patients were prescribed prophylaxis at every visit, 31.7% were on an on-demand regimen. Patients with severe haemophilia A on prophylaxis (n = 82) had a mean annual rate of treated bleeds of 2.8 ± 4.4, whereas it was 19.1 ± 32.0 for the on-demand group (n = 31), and a mean total Gilbert Score of 9.9 ± 10.3 at baseline and 4.1 ± 6.7 at study end; vs. 15.2 ± 17.3 and 13.7 ± 17.1 for on-demand respectively. The majority of the bleeds (91.1%) were treated with one or two infusions. Four patients without inhibitor history had a first positive inhibitor test during the study. This study demonstrates the effective use of rFVIII-FS in emerging countries and adds to the established safety profile of rFVIII-FS.

Continuous infusion of recombinant factor VIII formulated with sucrose in surgery: non-interventional, observational study in patients with severe haemophilia A.

In haemophilia A, continuous infusion (CI) of FVIII perioperatively provides a more constant FVIII level than conventional bolus injections, avoiding low trough levels that could increase bleeding risk. Due to the low number of surgical cases in clinical trials, especially in haemophilia, more information on the clinical practice of CI from observational studies is helpful. We aimed to evaluate the effectiveness and safety of CI with recombinant factor VIII formulated with sucrose (rFVIII-FS) in a typical surgery practice setting. This was a non-interventional study in 12 centres. Patients with severe haemophilia A who received rFVIII-FS by CI during and after surgery were included in this study if they had more than 150 exposure days (EDs) to any FVIII product and had no history of inhibitors before CI. Patients were observed during the entire course of CI, with monitoring up to 3 months thereafter. Twenty-five patients with 28 surgeries were included in the analysis. Median age was 51.7 (range 10-75). Most (75%; 21/25) patients underwent orthopaedic surgeries. The median dose of rFVIII-FS consumed during CI was 376 IU kg(-1) (range 157.9-3605.6 IU kg(-1)) with a greater median dose for orthopaedic surgeries (424.0 IU kg(-1)) compared to non-orthopaedic surgeries (278.5 IU kg(-1)). 95% of all FVIII measurements (214/224) were on target. Efficacy and tolerability were rated as good/excellent in 89.3% (25/28) of surgeries. No inhibitors were observed during or after surgery. This study demonstrates the effectiveness of CI with rFVIII-FS during surgery in patients with severe haemophilia A in a clinical practice setting.

The state of the art in European research on reducing social exclusion and stigma related to mental health: a systematic mapping of the literature.

Stigma and social exclusion related to mental health are of substantial public health importance for Europe. As part of ROAMER (ROAdmap for MEntal health Research in Europe), we used systematic mapping techniques to describe the current state of research on stigma and social exclusion across Europe. Findings demonstrate growing interest in this field between 2007 and 2012. Most studies were descriptive (60%), focused on adults of working age (60%) and were performed in Northwest Europe-primarily in the UK (32%), Finland (8%), Sweden (8%) and Germany (7%). In terms of mental health characteristics, the largest proportion of studies investigated general mental health (20%), common mental disorders (16%), schizophrenia (16%) or depression (14%). There is a paucity of research looking at mechanisms to reduce stigma and promote social inclusion, or at factors that might promote resilience or protect against stigma/social exclusion across the life course. Evidence is also limited in relation to evaluations of interventions. Increasing incentives for cross-country research collaborations, especially with new EU Member States and collaboration across European professional organizations and disciplines, could improve understanding of the range of underpinning social and cultural factors which promote inclusion or contribute toward lower levels of stigma, especially during times of hardship.

Cervical spine injuries in children: a review of 103 patients treated consecutively at a level 1 pediatric trauma center.

PURPOSE: Cervical spine (C-spine) injuries occur infrequently in children but may be associated with significant disability and mortality. The purpose of this study was to review the experience of a level 1 pediatric trauma center to determine the epidemiology, risk factors, mechanisms, levels, types of injury, comorbid factors, and outcomes associated with these potentially devastating injuries. METHODS: A retrospective analysis of 103 consecutive C-spine injuries treated at a level 1 pediatric trauma center over a 9(1/2)-year period (January 1991 through August 2000) was performed. RESULTS: The mean age was 10.3 +/- 5.2 years, and the male-to-female ratio was 1.6:1. The most common mechanism of injury was motor vehicle related (52%), followed by sporting injuries (27%). Football injuries accounted for 29% of all sports-related injuries. Sixty-eight percent of all children sustained injuries to C1 to C4; 25% to C5 to C7; and 7% to both. Spinal cord injury without radiographic abnormality (SCIWORA) occurred in 38%. Five patients had complete cord lesions involving the lower C-spine (C4 to C7); 4 of these were motor vehicle related, and all 4 patients died. Isolated C-spine injuries occurred in 43%, whereas 38% had associated closed head injuries (CHI). The overall mortality rate was 18.5%, most commonly motor vehicle related (95%), occurring in younger children (mean and median age 5 years) and associated with upper C-spine injuries (74%) and CHI (89%). C1 dislocations occurred in younger children (mean age, 6.6 years), most often as a result of motor vehicle-related trauma (especially pedestrians) and were associated with the highest injury severity score (ISS), longest length of stay (LOS), most CHIs, and the highest mortality rate (50%). C-spine fractures with or without SCI occurred most commonly as a result of falls and dives. Sporting injuries occurred almost exclusively in adolescent boys (mean age, 13.8 years) and were isolated injuries associated with a relatively low ISS and shorter LOS. Interestingly, 75% of sporting injuries showed SCIWORA, and all infants suffering from child abuse had SCIWORA. CONCLUSIONS: Mechanisms of injury are age related, with younger children sustaining C-spine injuries as a result of motor vehicle-related trauma and older adolescents commonly injured during sporting activities. C-spine injuries in children most commonly involve the upper C-spine, but complete lesions of the cord are associated more frequently with lower C-spine injuries. The type of C-spine injury is related to the mechanism of injury: SCIWORA is associated with sporting activities and child abuse, C-spine dislocations most commonly result from motor vehicle-related trauma (especially among pedestrians), and C-spine fractures occur most commonly as a result of falls and dives. Predictors of mortality include younger age, motor vehicle-related mechanism, C1 dislocations, high ISS greater than 25, and associated CHI. A high index of suspicion for SCIWORA is essential when evaluating adolescents with neck trauma associated with sporting injuries or victims of child abuse.

Frequency of genotypic and phenotypic drug-resistant HIV-1 among therapy-naive patients of the German Seroconverter Study.

Genotypic and phenotypic resistance of viral reverse transcriptase (RT) and protease (PR) was determined for 64 therapy-naive, HIV-1-infected seroconverters of the German Seroconverter Study coordinated by the Robert Koch-Institut, Berlin. The date of seroconversion of patients and the laboratory, clinical, and therapeutic follow-up data were documented. Samples were collected between 1996 and 1999. Phenotypic resistant HIV-1 were found in 8 (13%) seroconverters; in most cases resistance was weak and mainly directed against RT inhibitors (4 nucleoside reverse transcriptase inhibitors [NRTIs], 2 nonnucleoside reverse transcriptase inhibitors [NNRTIs], 1 combination NRTI/NNRTI). Only one infection with a weak PR inhibitor resistance was identified. Transmission of multidrug-resistant HIV-1 has not yet been observed. Frequently at least one or more amino acid mutations associated with antiretroviral drug resistance were detected by genotypic analysis. The mean number of resistance-associated mutations in the RT of the transmitted virus has increased significantly since 1996. Studies have shown the improved benefit of initial antiretroviral therapy if based on genotypic resistance data. In view of the considerably high level of transmission of resistant HIV-1 in Germany, which is also seen in other studies in Europe and the United States, we suggest determining the genotypic resistance pattern before starting therapy of newly HIV-1-infected patients.