Health related quality of life measure in systemic pediatric rheumatic diseases and its translation to different languages: an international collaboration

Background: Rheumatic diseases in children are associated with significant morbidity and poor health-related quality of life (HRQOL). There is no health-related quality of life (HRQOL) scale available specifically for children with less common rheumatic diseases. These diseases share several features with systemic lupus erythematosus (SLE) such as their chronic episodic nature, multi-systemic involvement, and the need for immunosuppressive medications. HRQOL scale developed for pediatric SLE will likely be applicable to children with systemic inflammatory diseases.Findings: We adapted Simple Measure of Impact of Lupus Erythematosus in Youngsters (SMILEY (c)) to Simple Measure of Impact of Illness in Youngsters (SMILY (c)-Illness) and had it reviewed by pediatric rheumatologists for its appropriateness and cultural suitability. We tested SMILY (c)-Illness in patients with inflammatory rheumatic diseases and then translated it into 28 languages. Nineteen children (79% female, n= 15) and 17 parents participated. the mean age was 12 +/- 4 years, with median disease duration of 21 months (1-172 months). We translated SMILY (c)-Illness into the following 28 languages: Danish, Dutch, French (France), English (UK), German (Germany), German (Austria), German (Switzerland), Hebrew, Italian, Portuguese (Brazil), Slovene, Spanish (USA and Puerto Rico), Spanish (Spain), Spanish (Argentina), Spanish (Mexico), Spanish (Venezuela), Turkish, Afrikaans, Arabic (Saudi Arabia), Arabic (Egypt), Czech, Greek, Hindi, Hungarian, Japanese, Romanian, Serbian and Xhosa.Conclusion: SMILY (c)-Illness is a brief, easy to administer and score HRQOL scale for children with systemic rheumatic diseases. It is suitable for use across different age groups and literacy levels. SMILY (c)-Illness with its available translations may be used as useful adjuncts to clinical practice and research.Rutgers State Univ, Robert Wood Johnson Med Sch, New Brunswick, NJ 08903 USARutgers State Univ, Child Hlth Inst New Jersey, New Brunswick, NJ 08901 USAHosp Special Surg, New York, NY 10021 USAUniv Michigan, Ann Arbor, MI 48109 USARed Cross War Mem Childrens Hosp, Cape Town, South AfricaAin Shams Univ, Pediat Allergy Immunol & Rheumatol Unit, Cairo, EgyptAin Shams Univ, Pediat Rheumatol Pediat Allergy Immunol & Rheum, Cairo, EgyptKing Faisal Specialist Hosp & Res Ctr, Riyadh 11211, Saudi ArabiaCharles Univ Prague, Prague, Czech RepublicGen Univ Hosp, Prague, Czech RepublicUniv Hosp Motol, Dept Pediat, Prague, Czech RepublicAarhus Univ, Hosp Skejby, Aarhus, DenmarkRigshosp, Juliane Marie Ctr, DK-2100 Copenhagen, DenmarkUniv Med Ctr, Dept Pediat Immunol, Utrecht, NetherlandsWilhelmina Childrens Hosp, Utrecht, NetherlandsGreat Ormond St Hosp Sick Children, Children NHS Fdn Trust, Renal Unit, London, EnglandLyon Univ, Hosp Civils Lyon, Rheumatol & Dermatol Dept, Lyon, FranceMed Univ Innsbruck, A-6020 Innsbruck, AustriaPrim Univ Doz, Bregenz, AustriaHamburg Ctr Pediat & Adolescence Rheumatol, Hamburg, GermanyAsklepios Clin Sankt, Augustin, GermanyUniv Zurich, Childrens Hosp, Zurich, SwitzerlandAristotle Univ Thessaloniki, Pediat Immunol & Rheumatol Referral Ctr, GR-54006 Thessaloniki, GreeceIsrael Meir Hosp, Kefar Sava, IsraelSanjay Gandhi Postgrad Inst Med Sci, Lucknow, Uttar Pradesh, IndiaSemmelweis Univ, H-1085 Budapest, HungaryAnna Meyer Hosp, Florence, ItalyUniv Siena, Res Ctr System Autoimmune & Autoinflammatory Dis, I-53100 Siena, ItalyUniv Florence, Florence, ItalyOsped Pediat Bambino Gesu, IRCCS, Pediat Rheumatol Unit, Rome, ItalyUniv Genoa Pediat II Reumatol, Ist G Gaslini EULAR, Ctr Excellence Rheumatol, Genoa, ItalyUniv Cattolica Sacro Cuore, Inst Pediat, Rome, ItalyUniv Padua, Dept Pediat, Pediat Rheumatol Unit, Padua, ItalyYokohama City Univ, Sch Med, Yokohama, Kanagawa 232, JapanUniv Estadual Paulista, UNESP, Botucatu, SP, BrazilUniversidade Federal de São Paulo, Dept Pediat, São Paulo, BrazilUniv Estadual Campinas, Dept Med, Campinas, SP, BrazilUniv Fed Rio de Janeiro, Dept Pediat, Rio de Janeiro, BrazilUniv Estado do, Adolescent Hlth Care Unit, Div Pediat Rheumatol, Rio de Janeiro, BrazilUniv São Paulo, Fac Med, Childrens Inst, Dept Pediat,Pediat Rheumatol Unit, São Paulo, BrazilChildrens Inst, Pediat Rheumatol Unit, São Paulo, BrazilClin Pediat I, Cluj Napoca, RomaniaInst Rheumatol, Belgrade, SerbiaUniv Childrens Hosp, Univ Med Ctr Ljubljana, Ljubljana, SloveniaHead Rheumatol Hosp Pedro Elizalde, Buenos Aires, DF, ArgentinaHosp Gen Mexico City, Mexico City, DF, MexicoHosp Infantil Mexico Fed Gomez, Mexico City, DF, MexicoHosp San Juan Dios, Barcelona, SpainHosp Univ Valle Hebron, Barcelona, SpainMt Sinai Med Ctr, New York, NY 10029 USAMt Sinai Med Ctr, Miami Beach, FL 33140 USAComplejo Hosp Univ Ruiz & Paez, Bolivar, VenezuelaHacettepe Univ, Dept Pediat, Ankara, TurkeyIstanbul Univ, Cerrahpasa Med Sch, Istanbul, TurkeyFMF Arthrit Vasculitis & Orphan Dis Res Ctr, Inst Hlth Sci, Ankara, TurkeyUniv Calgary, Dept Pediat, Alberta Childrens Hosp, Res Inst, Calgary, AB T2N 1N4, CanadaUniversidade Federal de São Paulo, Dept Pediat, São Paulo, BrazilWeb of Scienc

IgG2 Antibodies against a Clinical Grade Plasmodium falciparum CSP Vaccine Antigen Associate with Protection against Transgenic Sporozoite Challenge in Mice

The availability of a highly purified and well characterized circumsporozoite protein (CSP) is essential to improve upon the partial success of recombinant CSP-based malaria vaccine candidates. Soluble, near full-length, Plasmodium falciparum CSP vaccine antigen (CS/D) was produced in E. coli under bio-production conditions that comply with current Good Manufacturing Practices (cGMP). A mouse immunogenicity study was conducted using a stable oil-in-water emulsion (SE) of CS/D in combination with the Toll-Like Receptor 4 (TLR4) agonist Glucopyranosyl Lipid A (GLA/SE), or one of two TLR7/8 agonists: R848 (un-conjugated) or 3M-051 (covalently conjugated). Compared to Alum and SE, GLA/SE induced higher CS/D specific antibody response in Balb/c mice. Subclass analysis showed higher IgG2:IgG1 ratio of GLA/SE induced antibodies as compared to Alum and SE. TLR synergy was not observed when soluble R848 was mixed with GLA/SE. Antibody response of 3M051 formulations in Balb/c was similar to GLA/SE, except for the higher IgG2:IgG1 ratio and a trend towards higher T cell responses in 3M051 containing groups. However, no synergistic enhancement of antibody and T cell response was evident when 3M051 conjugate was mixed with GLA/SE. In C57Bl/6 mice, CS/D adjuvanted with 3M051/SE or GLA/SE induced higher CSP repeat specific titers compared to SE. While, 3M051 induced antibodies had high IgG2c:IgG1 ratio, GLA/SE promoted high levels of both IgG1 and IgG2c. GLA/SE also induced more potent T-cell responses compared to SE in two independent C57/BL6 vaccination studies, suggesting a balanced and productive TH1/TH2 response. GLA and 3M-051 similarly enhanced the protective efficacy of CS/D against challenge with a transgenic P. berghei parasite and most importantly, high levels of cytophilic IgG2 antibodies were associated with protection in this model. Our data indicated that the cGMP-grade, soluble CS/D antigen combined with the TLR4-containing adjuvant GLA/SE warrants further evaluation for protective responses in humans

The challenges of transferring chronic illness patients to adult care: reflections from pediatric and adult rheumatology at a US academic center

<p>Abstract</p> <p>Background</p> <p>Little is known about the transfer of care process from pediatric to adult rheumatology for patients with chronic rheumatic disease. The purpose of this study is to examine changes in disease status, treatment and health care utilization among adolescents transferring to adult care at the University of California San Francisco (UCSF).</p> <p>Methods</p> <p>We identified 31 eligible subjects who transferred from pediatric to adult rheumatology care at UCSF between 1995–2005. Subject demographics, disease characteristics, disease activity and health care utilization were compared between the year prior to and the year following transfer of care.</p> <p>Results</p> <p>The mean age at the last pediatric rheumatology visit was 19.5 years (17.4–22.0). Subject diagnoses included systemic lupus erythematosus (52%), mixed connective tissue disease (16%), juvenile idiopathic arthritis (16%), antiphospholipid antibody syndrome (13%) and vasculitis (3%). Nearly 30% of subjects were hospitalized for disease treatment or management of flares in the year prior to transfer, and 58% had active disease at the time of transfer. In the post-transfer period, almost 30% of subjects had an increase in disease activity. One patient died in the post-transfer period. The median transfer time between the last pediatric and first adult rheumatology visit was 7.1 months (range 0.7–33.6 months). Missed appointments were common in the both the pre and post transfer period.</p> <p>Conclusion</p> <p>A significant percentage of patients who transfer from pediatric to adult rheumatology care at our center are likely to have active disease at the time of transfer, and disease flares are common during the transfer period. These findings highlight the importance of a seamless transfer of care between rheumatology providers.</p

Neurocognitive Dysfunction in Systemic Lupus Erythematosus: Association with Antiphospholipid Antibodies, Disease Activity and Chronic Damage

Introduction: Systemic lupus erythematosus (SLE) is characterized by frequent neuropsychiatric involvement, which includes cognitive impairment (CI). We aimed at assessing CI in a cohort of Italian SLE patients by using a wide range of neurocognitive tests specifically designed to evaluate the fronto-subcortical dysfunction. Furthermore, we aimed at testing whether CI in SLE is associated with serum autoantibodies, disease activity and chronic damage. Methods: Fifty-eight consecutive patients were enrolled. Study protocol included data collection, evaluation of serum level

The Pseudomonas aeruginosa Chemotaxis Methyltransferase CheR1 Impacts on Bacterial Surface Sampling

The characterization of factors contributing to the formation and development of surface-associated bacterial communities known as biofilms has become an area of intense interest since biofilms have a major impact on human health, the environment and industry. Various studies have demonstrated that motility, including swimming, swarming and twitching, seems to play an important role in the surface colonization and establishment of structured biofilms. Thereby, the impact of chemotaxis on biofilm formation has been less intensively studied. Pseudomonas aeruginosa has a very complex chemosensory system with two Che systems implicated in flagella-mediated motility. In this study, we demonstrate that the chemotaxis protein CheR1 is a methyltransferase that binds S-adenosylmethionine and transfers a methyl group from this methyl donor to the chemoreceptor PctA, an activity which can be stimulated by the attractant serine but not by glutamine. We furthermore demonstrate that CheR1 does not only play a role in flagella-mediated chemotaxis but that its activity is essential for the formation and maintenance of bacterial biofilm structures. We propose a model in which motility and chemotaxis impact on initial attachment processes, dispersion and reattachment and increase the efficiency and frequency of surface sampling in P. aeruginosa