Relationship between health-related quality of life, disease activity and disease damage in a prospective international multicenter cohort of childhood onset systemic lupus erythematosus patients.

Previously, we described associations between health-related quality of life (HRQOL) and disease-related factors among childhood onset systemic lupus erythematosus (cSLE) patients. Here we determined the relationship between HRQOL, disease activity and damage in a large prospective international cohort of cSLE. We compared HRQOL, disease activity and disease damage across different continents and examined the relationship between children's and parents' assessments of HRQOL. Patients with cSLE and their parents completed HRQOL measures at enrollment and ≥4 follow-up visits. Physicians assessed disease activity and damage. The multinational cohort ( n = 467) had relatively low disease activity and damage. Patient and parent HRQOL scores were significantly correlated. Asian and European patients had the highest HRQOL, while South and North American patients had lower HRQOL scores. Renal, CNS, skin and musculoskeletal systems exhibited the highest levels of damage. North and South American and Asian patients were more likely to have disease damage and activity scores above median values, compared with Europeans. Asians were more likely to use cyclophosphamide/rituximab. Female gender, high disease activity and damage, non-White ethnicity, and use of cyclophosphamide and/rituximab were related to lower HRQOL. HRQOL domain scores continue to emphasize that SLE has widespread impact on all aspects of children's and parents' lives.

Validation of the Portuguese Simple Measure of Impact of Lupus Erythematosus in Youngsters (SMILEY) in Brazil.

BACKGROUND AND OBJECTIVE: Simple Measure of the Impact of Lupus Erythematosus in Youngsters (SMILEY) is a health-related quality of life (HRQOL) assessment tool for pediatric systemic lupus erythematosus (SLE), which has been translated into Portuguese for Brazil. We are reporting preliminary data on cross-cultural validation and reliability of SMILEY in Portuguese (Brazil). METHODS: In this multi-center cross-sectional study, Brazilian children and adolescents 5-18 years of age with SLE and parents participated. Children and parents completed child and parent reports of Portuguese SMILEY and Portuguese Pediatric Quality of Life Inventory (PedsQL™) Generic and Rheumatology modules. Parents also completed the Childhood Health Assessment Questionnaire (CHAQ). Physicians completed the SLE disease activity index (SLEDAI), Physician's Global Assessment of disease activity (PGA) and Systemic Lupus Erythematosus International Collaborating Clinics ACR Damage Index (SDI). RESULTS: 99 subjects (84 girls) were enrolled; 93 children and 97 parents filled out the SMILEY scale. Subjects found SMILEY relevant and easy to understand and completed SMILEY in 5-15 minutes. Brazilian SMILEY was found to have good psychometric properties (validity and reliability), and the child-parent agreement was moderate. CONCLUSION: SMILEY may eventually be used routinely as a research/clinical tool in Brazil. It may be also adapted for other Portuguese-speaking nations offering critical information regarding the effect of SLE on HRQOL for children with SLE.

An update on cross-cultural adaptation of US English SMILEY.

We previously developed a health-related quality of life (HRQOL) tool for children with systemic lupus erythematosus (SLE) that is valid in English for the United States, called Simple Measure of Impact of Lupus Erythematosus in Youngsters (SMILEY). In order to determine the effect of SLE on the well-being of children, adolescents and their parents and examine the response to treatment modalities, it is critical to have an HRQOL tool that is applicable for different cultures. After validation in US English, we reported the translation and cultural adaptation process undertaken by our team to make SMILEY available in the following 13 accepted modern language variants: Danish, Dutch, French (France), German (Germany), Hebrew, Italian, Portuguese (Brazil), Slovene, Spanish (USA and Puerto Rico), Spanish (Spain), Spanish (Argentina), Spanish (Mexico) and Turkish. In this report we will describe the translation and adaptation of SMILEY into Afrikaans, Xhosa, Arabic (Saudi Arabia), Arabic (Egypt), Chinese, Czech, English (UK), German (Austria), German (Switzerland), Greek, Hindi, Hungarian, Japanese, Romanian, Serbian and Spanish for Venezuela. We followed the earlier reported procedure in this study consisting of: establishing collaborative relationships with different physicians caring for children with rheumatic diseases; forward and back translation of SMILEY and revisions; and cultural adaptation of SMILEY content.

Worldwide incidence and prevalence of pediatric onset systemic lupus erythematosus.

Compilation of worldwide data regarding the incidence and prevalence of pediatric-onset systemic lupus erythematosus (SLE) is needed in order to evaluate the scope of the disease in the pediatric population. A literature review was performed to unify the current data available on the global incidence and prevalence of pediatric-onset SLE. We examined 13 available epidemiological studies concentrated on the incidence and prevalence of pediatric-onset SLE. The available reports were predominantly from North America, Europe and Asia. The limited amount of studies available highlights the need for more epidemiological research in order to better comprehend the global scope of this disease.

MicroCT morphometry analysis of mouse cancellous bone: intra- and inter-system reproducibility.

The agreement between measurements and the relative performance reproducibility among different microcomputed tomography (microCT) systems, especially at voxel sizes close to the limit of the instruments, is not known. To compare this reproducibility 3D morphometric analyses of mouse cancellous bone from distal femoral epiphyses were performed using three different ex vivo microCT systems: GE eXplore Locus SP, Scanco µCT35 and Skyscan 1172. Scans were completed in triplicate at 12 µm and 8 µm voxel sizes and morphometry measurements, from which relative values and dependence on voxel size were examined. Global and individual visually assessed thresholds were compared. Variability from repeated scans at 12 µm voxel size was also examined. Bone volume fraction and trabecular separation values were similar, while values for relative bone surface, trabecular thickness and number varied significantly across the three systems. The greatest differences were measured in trabecular thickness (up to 236%) and number (up to 218%). The relative dependence of measurements on voxel size was highly variable for the trabecular number (from 0% to 20% relative difference between measurements from 12 µm and 8 µm voxel size scans, depending on the system). The intra-system reproducibility of all trabecular measurements was also highly variable across the systems and improved for BV/TV in all the systems when a smaller voxel size was used. It improved using a smaller voxel size in all the other parameters examined for the Scanco system, but not consistently so for the GE or the Skyscan system. Our results indicate trabecular morphometry measurements should not be directly compared across microCT systems. In addition, the conditions, including voxel size, for trabecular morphometry studies in mouse bone should be chosen based on the specific microCT system and the measurements of main interest.

Impact of lupus on school attendance and performance.

Cognitive impairment in children and adolescents with systemic lupus erythematosus (SLE) can affect intelligence, academic achievement, arithmetic, reading comprehension, learning, visual memory and complex problem solving ability. In this prospective two-center study, we examined children's (and adolescents') and parents' perception of the impact of SLE on school; the relationship between child and parent reports on school-related issues; and the relationship between health-related quality of life (HRQOL) and school-related issues. Patients aged 9-18 years with SLE and their parents completed corresponding child and parent reports of the SLE-specific HRQOL scale, Simple Measure of Impact of Lupus Erythematosus in Youngsters (SMILEY), and PedsQL(TM) generic and rheumatology modules. Patients also completed questions related to school attendance and performance. Qualified physicians assessed SLE activity, damage and severity. Forty-one patients (73% girls) with SLE with mean age of 15 +/- 3 years and 32 parents participated. Mean school domain scores for child and parent reports of the PedsQL( TM) generic report were lower compared with total and subscale scores. Patients reported difficulty with schoolwork, had problems with memory and concentration, and were sad about the effect of SLE on schoolwork and attendance. Moderate to strong correlations were found between child and parent reports on school-related items from all questionnaires. Eighty-three percent of patients felt that they would have done better in school if they did not have SLE. Moderate correlations (r = 0.3-0.4) were found between SMILEY total score and the following items: satisfaction with school performance, interest in schoolwork, remembering what was learned, and concentrating in class. Patients on intravenous chemotherapeutic medications missed more school days (p < 0.05) compared with patients on oral medications. Also, patients with a greater number of missed school days had increased disease activity (p = 0.008). SLE and activities related to caring for the disease clearly impose a burden on children's school attendance and performance. School-related activities can have a significant impact on HRQOL in children and adolescents with SLE. Detailed examination of the impact of SLE on attendance and the various aspects of school performance will enable us to formulate interventions in school for these children and adolescents.

Preliminary cross-cultural adaptation of a new pediatric health-related quality of life scale in children with systemic lupus erythematosus: an international effort.

We developed a brief, new health-related quality of life measure for children with systemic lupus erythematosus that is valid in English for the United States, called Simple Measure of Impact of Lupus Erythematosus in Youngsters (SMILEY). The United States-English language questionnaire may not be applicable to most of the countries in the world and several United States population subgroups, such as Hispanics. In order to measure the impact of morbidity of systemic lupus erythematosus on the lives of children, adolescents, and their parents and assess the outcome of new therapies, it is critical to have a uniform measure of systemic lupus erythematosus-specific health-related quality of life that is valid for different cultures. We report the translation and cultural adaptation process undertaken by our team with the goal of cross-cultural validation of SMILEY in the following thirteen languages: Danish, Dutch, French (France), German (Germany), Hebrew, Italian, Portuguese (Brazil), Slovene, Spanish (USA and Puerto Rico), Spanish (Spain), Spanish (Argentina), Spanish (Mexico), and Turkish. We employed the following steps: establishing collaborative relationships with institutions across the globe; forward and back translation of SMILEY text; and cultural adaptation of SMILEY content. We are in the process of enrolling patients and conducting validation of the translated and adapted versions of SMILEY.

Relationship between health-related quality of life and SLE activity and damage in children over time.

We previously described the development and validation of the 'Simple Measure of the Impact of Lupus Erythematosus in Youngsters' (SMILEY) for the reliable assessment of health-related quality of life (HRQOL) in children with systemic lupus erythematosus (SLE). The objectives of this new study were to determine the relationship of SMILEY scores to patient's/parent's assessment of HRQOL and SLE status, and physician's assessment of disease activity and damage over time. In this multicentre study, 68 children with SLE and parents completed SMILEY including the global HRQOL and SLE status assessments, physicians completed disease activity and damage tools at two time-points. Spearman rho was calculated between SMILEY scores and other scales, and between interval changes in SMILEY scores and other scales. SMILEY scores correlated with patient/parent assessments of global HRQOL and SLE status, disease activity and damage, confirming previous findings. The change in disease activity and damage measures correlated most strongly with the changes in SMILEY domains, Limitation and Burden of SLE. Results provide preliminary evidence that Limitation and Burden of SLE domains of SMILEY reflect the impact of disease activity and damage on HRQOL.

Do children with lupus have fewer male siblings?

It is widely acknowledged that genetic factors play a significant role in the pathogenesis of systemic lupus erythematosus (SLE). However, the female preponderance remains unexplained. We hypothesized that the female preponderance in childhood SLE results from selection early in the course of conception against male fetuses bearing genetic material predisposing to SLE. If this hypothesis is accurate, there should be a decreased number of male children in families with a child with SLE. Alternatively, children with SLE would have fewer male siblings. Further, this hypothesis may apply to other diseases with a female predominance such as pauciarticular onset juvenile rheumatoid arthritis (PaJRA), and not apply to diseases without female preponderance such as systemic onset juvenile rheumatoid arthritis (SoJRA). Chart review of patients with childhood onset SLE and PaJRA revealed a greater number of female children in these families compared with families of patients with SoJRA. Large-scale epidemiologic studies with precise counting of miscarriages and abortions could help to confirm these findings. Detailed studies of genetic and maternal intrauterine factors are required to conclusively prove this hypothesis.

Quality of life in children with systemic lupus erythematosus: a review.

Systemic lupus erythematosus (SLE) in children is a chronic multisystem disease with wide ranging effects on their quality of life (QOL). While SLE's impact on different arenas of life and well-being has been extensively examined in the adult population, its effect on children has not received adequate attention. This review discusses the multidimensional aspect of QOL, the biopsychosocial implications of SLE, factors complicating QOL measurement in the affected population, and the different generic and disease-specific scales used for measuring QOL and related constructs. Until now, there have not been any pediatric SLE-specific health-related QOL (HRQOL) scales. A section is devoted to a novel instrument developed specifically for measuring QOL in pediatric lupus called the Simple Measure of the Impact of Lupus Erythematosus in Youngsters (SMILEY). SMILEY is a brief, easily understood, valid, reliable and internally consistent pediatric SLE-specific QOL scale and will be a useful adjunct to clinical trials and outcomes research.

SAR studies on a novel series of human cytomegalovirus primase inhibitors.

A novel series of imidazolylpyrimidines were found to possess inhibitory activity against the human CMV UL70 primase. Extensive SAR studies on an HTS lead led to potent, orally bioavailable compounds with anti-CMV IC(50) values of 150 nM in both viral yield and viral DNA replication assays and with a much reduced cytotoxicity compared to marketed treatments ganciclovir and cidofovir.

Maturational changes in dentin mineral properties.

In this study the changes in properties of the maturing mantle and circumpulpal dentin were quantitatively analyzed. Sections from six fetal bovine undecalcified incisors were used. Regions of mantle and circumpulpal dentin of sequential maturation stages were identified on spectroscopic images acquired by Fourier Transform Infrared Imaging. Spectroscopic parameters corresponding to mineral properties at these stages were analyzed and reported as a function of distance from the cervix of the incisor, the latter representing tissue age. Mineral parameters were correlated with distance from the cervix. Values of these parameters in mantle and circumpulpal dentin were compared. A multi-phasic pattern of changes was found for all the parameters examined, with most of the alterations occurring in the initial maturation period. The patterns of temporal variation in mantle and circumpulpal dentin mineral properties show distinct developmental stages and were not identical for the two dentin compartments. The study showed that mineral maturation in dentin is not a linear process and that mantle dentin is developmentally distinct from circumpulpal dentin, presenting at certain stages different physicochemical events during the maturation of the tissue.

Discovery of a novel series of inhibitors of human cytomegalovirus primase.

Infection by human cytomegalovirus (hCMV) remains a potent threat to susceptible people throughout the world. We have discovered a series of imidazolyl-pyrimidine compounds, which were found to be irreversible inhibitors of the hCMV UL70 primase based on results from radiolabeling and SAR studies. Two promising analogs are described that rival ganciclovir and cidofovir in antiviral potency and possess improved cytotoxicity profiles.

Prolonged operative time correlates with increased infection rate after total knee arthroplasty.

Risk stratification has proven to be a useful tool in surgical site infection prevention. The duration of the surgical procedure has been recommended for use in surgical site infection (SSI) risk stratification (Infect Control Hosp Epidemiol 20:247-248, 1999). A retrospective analysis of 6489 patients who underwent total knee replacement (TKR) between 1993 and 1999 assessed the association between the duration of the surgical procedure and the risk of postoperative infection. One hundred thirteen infected patients were matched with 236 controls, and nominal variables were statistically processed. Patients without infections (n = 236) had surgery durations of 94 +/- 28 min, and patients with infection (n = 104) had durations of 127 +/- 45 min (p < 0.001). Operation time has positive correlations with weight (r = 0.3, p < 0.001), body mass index (r = 0.3, p < 0.001), and the total number of comorbidities (r = 0.2, p < 0.001; n = 340). The results confirm that the duration of the surgical procedure can be used as a risk predictor for SSI in TKR.

A new technique to improve cup inclination accuracy in primary total hip arthroplasty.

Accurate inclination and anteversion of the acetabular component is paramount to achieve a stable total hip arthroplasty, prevent prosthetic dislocation and minimize long- term wear. We present and evaluate a simple new technique to improve consistency in cup inclination during primary total hip arthroplasty, based on information available from the preoperative plan. The technique consists of assessing the distance and relationship between the inferomedial border of the acetabular cup and the inferomedial margin of the teardrop, with the use of a measuring probe. This simple surgical gesture improved consistency in cup inclination during total hip arthroplasty.;

Quality of life in paediatric lupus.

Paediatric systemic lupus erythematosus (SLE) is associated with significant morbidity and has biopsychosocial implications resulting from the disease and its treatment. The aim of this study was to identify domains of quality of life (QOL) impacted by SLE in children. Children with SLE and their parents were asked a single open-ended question related to lupus. Themes derived from children's responses focused primarily on coping and maintaining control of their life despite SLE. Themes from the parents' responses were twofold: a) efforts to cope with their child having SLE; and b) appreciation/sadness in connection with their children's coping process. Qualitative exploration of different facets of QOL in these children is critical for the understanding of specific factors that assist/ease the coping process and formulating interventions for improving children's/family's self-efficacy and disease management.

Age affects the perception of limb length discrepancy in patients with and without a total hip arthroplasty.

The amount of lengthening or shortening that can be detected by patients before and after total hip arthroplasty has not been yet quantified. We studied the ability to detect limb length inequality in 194 patients with and without a total hip arthroplasty, match-paired for age and sex. None of the participants had clinical signs of lumbosacral pathology, spinal deformity, or fixed pelvic obliquity; and all had equal functional and actual limb length. The participants walked with shoes, with and without the addition of fixed insoles, to simulate 2.5, 5, 10 and 15 millimeters of shortening and lengthening of the tested limb. Lengthening and shortening were similarly detected. Younger individuals detected the differences better than older ones (p=0.001), and there was a significant correlation between the decade of life and the ability to detect a limb length discrepancy (r=-0.22; p=0.002). This study demonstrates that perception of limb length is affected by the age, with older individuals having less awareness of changes in limb length than younger ones. (Hip International 2004; 14: 249-53).

The day of discharge after total hip arthroplasty and the achievement of rehabilitation functional milestones: 11-year trends.

This is a report on 11 years (1990-2000) of total hip arthroplasty cases and days of discharge from one large city hospital. In 1990, patients stayed an average of 9.7 days after surgery. By 2000, patients stayed only 5.3 days. In general, women stayed longer than men, but this gap had nearly disappeared by 2000. The patients discharged in 2000 achieved fewer functional milestones during their hospital stay than those discharged in 1990.

A cross-sectional study of clinical thrombotic risk factors and preventive treatments in antiphospholipid syndrome.

OBJECTIVE: Antiphospholipid antibodies (aPL) are major risk factors for thrombosis. Other clinical factors exist in antiphospholipid syndrome (APS) patients which may have an additive or preventive effect on thrombosis. We therefore performed a cross-sectional study to analyse additive clinical thrombotic risk factors and possible preventive treatments in APS patients, and to compare the results with those obtained in asymptomatic aPL-positive (no history of vascular thrombosis or pregnancy morbidity) patients. METHODS: We identified 77 APS patients with non-gravid thrombotic events (group A) and 56 asymptomatic aPL-positive patients (group B). The study periods were defined as 6 months prior to the time of first vascular event in group A and 6 months prior to the patient's last visit in group B. Medical records were reviewed to evaluate the incidence of hypertension, diabetes mellitus, hypercholesterolaemia, regular cigarette smoking, oral contraceptive use or hormone replacement therapy, surgical procedures, pregnancy with or without an APS-related event, malignancy and infections. In addition, any history of thrombocytopenia or the use of aspirin, hydroxychloroquine, corticosteroids or immunosuppressives during the study periods was recorded. Bivariate statistical analysis and logistic regression tests were performed to compare groups. RESULTS: In group A, 75% (n=58) of patients and in group B 48% (n=27) of patients had at least one of the additional risk factors during the study periods. In the bivariate analysis, pregnancy (P=0.005) and surgical procedures (P=0.04) were significantly more frequent in group A, while aspirin (P<0.001), hydroxychloroquine (P<0.001) and corticosteroids (P=0.002) were used significantly more frequently in group B. In logistic regression, the probability of an event was decreased by taking aspirin and/or hydroxychloroquine. In women only, the probability of an event was increased with thrombocytopenia and pregnancy or surgical procedures. The incidences of hypertension and smoking and the presence of more than one risk factor were significantly associated with arterial thrombosis but not venous thrombosis. CONCLUSION: While traditional risk factors were similar between groups, pregnancy and surgical procedures increased the risk of thrombosis. Hypertension and smoking were associated with arterial events. Possessing a combination of risk factors may increase the occurrence of arterial thrombosis but not venous thrombosis. Use of aspirin and/or hydroxychloroquine may be protective against thrombosis in asymptomatic aPL-positive individuals.

Measuring recovery after a hip fracture using the SF-36 and Cummings scales.

The objective of this study was to assess outcomes of traditional treatment of fractures using the SF-36 and the Cummings Hip Scale. In designing randomized clinical trials, it is necessary to determine the timing of assessment either for progress or for the main outcome. We set out to document the recovery of patients after surgery for hip fracture using current standard methods of medical care. This was a prospective study of a cohort of patients. Patients who were receiving standard medical care completed the SF-36 and the Cummings Hip Scale at previously determined times postoperatively. The SF-36 has eight subscales, including assessments of physical function, physical role behaviors, bodily pain, mental health, social role, emotional role, vitality and general health. Thirty-eight patients completed the questionnaires at 1 year postoperatively as well as previous time points. On the Cummings Hip Scale and the physical function, bodily pain, mental health, social function, emotional role, vitality and general health subscales of the SF-36, recovery is near complete at 6 months. Only the physical role subscale differs, with a statistically significant difference between the values at 6 months and 1 year, (p = 0.02). Patients attained over 90% of the 1 year value by 6 months for all except the physical role subscale. The physical role subscale reached 85%. For a hip fracture patient who is on the road to recovery, the majority of the recovery has therefore taken place by 6 months.