Articular chondrocytes embedded in alginate gel produce de novo a matrix rich in collagens and proteoglycans. A major advantage of this culture system is that the cells can be recovered by chelating ...the calcium, which otherwise maintains the alginate in its gel state. Chondrocytes thus released are surrounded by tightly bound cell-associated matrix, which seems to correspond to the pericellular and territorial matrices identified in cartilage by electron microscopy. The cells and their associated matrix can be easily separated by mild centrifugation from more soluble matrix components derived principally from the 'interterritorial' matrix. This new cell culture system thus makes it possible to study the assembly and turnover of molecules present in two distinct matrix pools. Importantly, a significant proportion of the aggrecan molecules in each of these two pools can be extracted using a non-denaturing solvent, thereby making possible studies of the metabolism and turnover of native proteoglycan aggregates. We show in this report that chondrocytes isolated from the full depth of adult bovine articular cartilage and maintained for 8 months in alginate gel are still metabolically active and continue to synthesize cartilage-specific type II collagen and aggrecan. The cells did not synthesize large amounts of type I collagen or of the small nonaggregating proteoglycans as usually occurs when chondrocytes lose their phenotypic stability. After this extended period of time in culture, the cells were present as two populations exhibiting differences in size, shape and amount of extracellular matrix surrounding them. The first population was found only near the surface of the bead: these cells were flattened and surrounded by a matrix sparse in proteoglycans and collagen fibrils. The second population was found throughout the remaining depth of the bead: the cells were more round and almost always surrounded by a basket-like meshwork consisting of densely packed fibrils running tangential to the surface.
Objective
To evaluate the responsiveness of Lupus Impact Tracker (LIT) to changes in physician and patient disease activity assessments over time.
Methods
Available longitudinal data from routine ...patient care visits on LIT, physician assessed disease activity (physician global assessment (PGA), SELENA-SLEDAI score, SELENA Flare Index (SFI)), and patient-reported changes in systemic lupus erythematosus (SLE) health status were analyzed. Significant, clinically important change (worsening or improvement) in physician disease activity assessment or patient-reported SLE health status were judged using the following criteria: change of 0.3 on PGA, 4 on SELENA-SLEDAI, change in SFI status over time, and change of 2 in either direction in patient-reported SLE health status. Mixed model regression analysis was used to compare changes in LIT using the above criteria.
Results
There were 1184 observations with significant changes in physician disease activity or patient-reported measure for 182 patients’ data across 1364 visits. Patients’ mean (SD) age and SELENA-SLEDAI were 43.5 (13.2) years and 6.4 (7.3) respectively. LIT mean scores decreased by more than 3 with improvement in PGA (standardized response mean −0.26, p < 0.05), while it increased by more than 5 with worsening in SELENA-SLEDAI (standardized response mean 0.42, p = 0.01). Mean change in LIT of greater than ±3 was noted with change in SFI status (p < 0.05). Mean LIT score decreased by greater than 4 and increased by greater than 2 with patient-reported improvement and worsening in SLE health status respectively (p < 0.05).
Conclusions
LIT is responsive to physician-assessed and patient-assessed changes in disease status. A mean LIT change of 2–4 may represent a significant clinical change in LIT. It is an effective tool that may be used by patients and physicians in tracking disease impact in SLE patients.
Background/purpose
To plan a quality improvement project, we need to understand the practice patterns of physicians. We undertook an online survey of systemic lupus erythematosus (SLE) patients and ...physicians providing care to SLE patients to determine the patterns of medical care provided to SLE patients.
Materials and methods
Two self-report surveys were developed. A 12-item survey for the patients and a 13-item survey for physicians enquired about longitudinal care for SLE. Surveys were administered online to physicians providing care to SLE patients, and to patients who self-identified as having SLE, through the Lupus Society of Illinois. Patient and physician data were analyzed for physician practice patterns for SLE care, using chi square tests and t tests. A P value of 0.05 or less was considered significant on two-tailed tests.
Results
A total of 283 patients completed the survey. Mean (SD) age and disease duration of patients were 45.9 (13.2) and 12.7 (9.7) years. Half of the participants were being seen at 3–4-month intervals. More than 70% of patients reported being tested for antinuclear antibody (ANA), and 20–30% anti-ENA antibody and Sjögren’s (SSA/SSB) antibodies, respectively, at each follow-up visit. Eighty-six rheumatologists completed the surveys. Mean (SD) age was 55 (12) years and 56% were men. More than half (54%) provided care only in a private practice setting. More than 80% of physicians reported seeing their SLE patients at 3–4-month interval. Only 2% reported performing ANA tests at each visit, while 4–5% performed anti-ENA and anti-SSA/SSB antibody tests at each visit for their SLE patients. More than 75% of physicians in private practice also ordered sedimentation rate at each visit for their SLE patients.
Conclusions
Unnecessary laboratory investigations may be being ordered routinely for patients at every visit. These results indicate a need for physician education on indications and utility of some of the laboratory tests such as ANA.
Objective
LupusPRO is a disease-targeted patient-reported outcome measure that was developed and validated among US patients with systemic lupus erythematosus (SLE). We report the cross-cultural ...validation results of the LupusPRO English-language version among Filipino SLE patients.
Method
The 43-item LupusPRO was pretested in 15 SLE individuals, then administered to 106 SLE patients, along with short-form SF36 and the EQ5D visual analogue scale. A mail/drop-back LupusPRO and change in health status item survey were returned within two to three days. Demographics, clinical and serological characteristics, disease activity and damage measured by PGA, SELENA-SLEDAI, LFA Flare, and SLICC-ACR SLE damage index (SDI) were collected. Internal consistency reliability (ICR), test-retest reliability (TRT), convergent validity (corresponding SF36 domains) and criterion validity (against general health and disease activity measures) were tested. Reported p values are two tailed.
Results
A total of 121 Filipino SLE subjects (95% women, median age 31.0 ± 16 years) with at least a high school level of English instruction participated. Median (IQR) PGA, SLEDAI and SDI were 0.0 (1.0), 2.0 (10) and 0 (1), respectively. ICR exceeded 0.7 for all domains except the lupus symptoms domain. TRT was greater than 0.85 for all LupusPRO domains. Convergent and criterion validity were observed against corresponding SF36 domains and disease activity measures. The tool was well received by patients. Confirmatory factor analysis showed good fit.
Conclusion
English LupusPRO has fair psychometric properties among SLE patients in the Philippines, and is now available for inclusion in clinical trials and longitudinal studies to test responsiveness to change.
Although treatments for osteoarthritis of the knee are often directed at relieving pain, pain may cause patients to alter how they perform activities to decrease the loads on the joints. The ...knee-adduction moment is a major determinant of the load distribution between the medial and lateral plateaus. Therefore, the interrelationship between pain and the external knee-adduction moment during walking may be especially important for understanding mechanical factors related to the progression of medial tibiofemoral osteoarthritis. Fifty-three subjects with symptomatic radiographic evidence of osteoarthritis of the knee were studied. These subjects were a subset of those enrolled in a double-blind study in which gait analysis and radiographic and clinical evaluations were performed after a 2-week washout of anti-inflammatory and analgesic treatment. The subjects then took a nonsteroidal anti-inflammatory drug, acetaminophen, or placebo for 2 weeks, and the gait and clinical evaluations were repeated. The change in the peak external adduction moment between the two evaluations was inversely correlated with the change in pain (R = 0.48, p < 0.001) and was significantly different between those whose pain increased (n = 7), decreased (n = 18), or remained unchanged (n = 28) (p = 0.009). Those with increased pain had a significant decrease in the peak external adduction (p = 0.005) and flexion moments (p = 0.023). In contrast, the subjects with decreased pain tended to have an increase in the peak external adduction moment (p = 0.095) and had a significant increase in the peak external extension moment (p = 0.017). The subjects whose pain was unchanged had no significant change in the peak external adduction (p = 0.757), flexion (p = 0.234), or extension (p = 0.465) moments. Thus, decreases in pain among patients with medial tibiofemoral osteoarthritis were related to increased loading of the degenerative portion of the joints. Additional long-term prospective studies are needed to determine whether increased loading during walking actually results in accelerated progression of the disease.
Summary
Objective To assess the capacity for research collaboration and implementation research in strengthening networks and institutions in developing countries.
Methods Bibliometric analysis of ...implementation research on diseases of poverty in developing countries from 2005 to 2010 through systematically searching bibliographic databases. Methods identified publication trends, participating institutions and countries and the cohesion and centrality of networks across diverse thematic clusters.
Results Implementation research in this field showed a steadily growing trend of networking, although networks are loose and a few institutions show a high degree of centrality. The thematic clusters with greatest cohesion were for tuberculosis and malaria.
Conclusions The capacity to produce implementation research on diseases of poverty is still low, with the prominence of institutions from developed countries. Wide ranges of collaboration and capacity strengthening strategies have been identified which should be put into effect through increased investments.
Objectif: Evaluer la capacité de collaboration de recherche et de la recherche sur l’implémentation dans le renforcement des réseaux et des institutions des pays en développement.
Méthodes: Analyse bibliométrique de la recherche sur l’implémentation dans les maladies de la pauvreté dans les pays en développement de 2005 à 2010 à travers la recherche systématique des bases de données bibliographiques. Les méthodes ont identifiées les tendances en matière de publications, les institutions et les pays participants et la cohésion et centralité des réseaux à travers divers groupes thématiques.
Résultats: La recherche sur l’implémentation dans ce domaine a montré une tendance en croissance continue des réseaux de collaboration bien que ceux‐ci soient lâches et que certaines institutions présentent un degréélevé de centralité. Les groupes thématiques avec la plus grande cohésion sont pour la tuberculose et le paludisme.
Conclusions: La capacité de produire une recherche sur l’implémentation pour les maladies de la pauvreté est encore faible, avec une proéminence des institutions des pays développés. De larges gammes de collaboration et de stratégies de renforcement de la capacité ont été identifiées, qui devraient être effectives à travers l’augmentation des investissements.
Objetivo: Evaluar la capacidad de colaboración y de investigación en la implementación en el fortalecimiento de las redes e instituciones de países en vías de desarrollo.
Métodos: Análisis bibliométrico de la investigación en la implementación en enfermedades relacionadas con la pobreza, en países en vías de desarrollo, entre el 2005 y el 2010 mediante una búsqueda sistemática de bases de datos bibliográficas. Los métodos identificaron tendencias, instituciones y países participantes y la cohesión y centralización de las redes a lo largo de diversos grupos temáticos.
Resultados: La implementación de la investigación en este campo mostró una tendencia creciente de interacción aunque las redes son débiles y pocas instituciones muestran un alto nivel de centralización. Los grupos temáticos con mayor cohesión eran los de tuberculosis y malaria.
Conclusiones: La capacidad de producir investigación sobre implementación para enfermedades relacionadas con la pobreza es aún baja, con el protagonismo de instituciones de países desarrollados. Se han identificado amplios rangos de colaboración y estrategias para el fortalecimiento de capacidades que deberían ponerse en marcha con mayores inversiones.
The Cancer and Leukemia Group B (CALGB) has been conducting a prospective cytogenetic companion study (CALGB 8461) to all CALGB treatment protocols for newly diagnosed adults with acute lymphoblastic ...leukemia (ALL). These protocols underwent a significant change in 1988 when a new intensive chemotherapy program was introduced (CALGB 8811). We asked whether karyotype continued to represent a significant prognostic factor in adult ALL patients after the change. A total of 256 patients had adequate pretreatment cytogenetic analyses: 67 before 1988 and 189 subsequently. The complete remission (CR) rate for the whole group was 80%. Patients with t(9;22), t(4;11), −7, or +8 had significantly lower probabilities of continuous CR and survival at 5 years (.11 and .12) than patients with a normal karyotype (.38 and .37) and patients with miscellaneous cytogenetic abnormalities (.52 and .49;P < .001 for each comparison). When analyzed by treatment period, the CR rate before CALGB 8811 was 63%; subsequently, it was 86% (P < .001). Patients with cytogenetic abnormalities other than t(9;22), t(4;11), −7, or +8 had better CR rates, disease-free survival (DFS), and survivals (P = .001,P = .04, and P = .004, respectively) after the change to the more intensive chemotherapy regimens. Patients with normal cytogenetics had improved CR rate but no improved DFS or survival, whereas no significant benefit for patients with t(9;22), t(4;11), −7, or +8 was seen. In a multivariate analysis, karyotype retained its prognostic significance for DFS but not for survival; it remained the most important factor for DFS. We conclude that cytogenetic analysis at diagnosis should be used to guide treatment decisions in adults with ALL.
Aims
Systemic lupus erythematosus (SLE) mostly affects young women, adversely affecting their quality of life (QOL). Caregivers may experience caregiver burden (CGB), and it may lower the quality of ...their relationship. Herein we studied caregiving and CGB and their effects on QOL and relationships in SLE.
Methods
We recruited 10 dyads from the Lupus Clinic. Data collected included demographics, CGB (CGB Scale, screen for CGB), QOL (SF-36) and the quality of the dyadic relationship (Dyadic Adjustment Scale (DAS)). We calculated correlation coefficients for associations between (i) CGB and (ii) dyadic QOL or DAS.
Results
The mean (± SD) age of SLE patients was 35.2 (± 9) years and of caregivers was 37.3 (± 9.64) years. The mean (± SD, min–max) total CGB score was 9.1 (± 5.8, 0–19). The caregiver's QOL correlated strongly with some of the domains of the patient's QOL. The SLE-related CGB was associated with the caregiver's own QOL and their SLE partner's QOL. The dyadic DAS was linked to the patient's QOL.
Conclusions
Because (i) CGB in SLE is associated with the caregiver's own QOL and with their SLE partner's QOL, and because (ii) the dyadic DAS score is linked primarily to the patient's QOL, then to optimize patient health outcomes and to decrease CGB, focus should be not only on the patient but should include the dyadic unit.
Significant findings: To optimize patient outcomes of SLE patients, focus should be on the dyadic unit. CGB in SLE is associated with the caregiver's own QOL and with the SLE partner's QOL, making it crucial to study this relationship in more detail.
Hexanucleotide repeat expansion in C9orf72 represents the most common genetic cause of familial and sporadic behavioural variant frontotemporal dementia. Previous studies show that some C9orf72 ...carriers with behavioural variant frontotemporal dementia exhibit distinctive atrophy patterns whereas others show mild or undetectable atrophy despite severe behavioural impairment. To explore this observation, we examined intrinsic connectivity network integrity in patients with or without the C9orf72 expansion. We studied 28 patients with behavioural variant frontotemporal dementia, including 14 C9orf72 mutation carriers (age 58.3 ± 7.7 years, four females) and 14 non-carriers (age 60.8 ± 6.9 years, four females), and 14 age- and sex-matched healthy controls. Both patient groups included five patients with comorbid motor neuron disease. Neuropsychological data, structural brain magnetic resonance imaging, and task-free functional magnetic resonance imaging were obtained. Voxel-based morphometry delineated atrophy patterns, and seed-based intrinsic connectivity analyses enabled group comparisons of the salience, sensorimotor, and default mode networks. Single-patient analyses were used to explore network imaging as a potential biomarker. Despite contrasting atrophy patterns in C9orf72 carriers versus non-carriers, patient groups showed topographically similar connectivity reductions in the salience and sensorimotor networks. Patients without C9orf72 expansions exhibited increases in default mode network connectivity compared to controls and mutation carriers. Across all patients, behavioural symptom severity correlated with diminished salience network connectivity and heightened default mode network connectivity. In C9orf72 carriers, salience network connectivity reduction correlated with atrophy in the left medial pulvinar thalamic nucleus, and this region further showed diminished connectivity with key salience network hubs. Single-patient analyses revealed salience network disruption and default mode network connectivity enhancement in C9orf72 carriers with early-stage or slowly progressive symptoms. The findings suggest that patients with behavioural variant frontotemporal dementia with or without the C9orf72 expansion show convergent large-scale network breakdowns despite distinctive atrophy patterns. Medial pulvinar degeneration may contribute to the behavioural variant frontotemporal dementia syndrome in C9orf72 carriers by disrupting salience network connectivity. Task-free functional magnetic resonance imaging shows promise in detecting early-stage disease in C9orf72 carriers and may provide a unifying biomarker across diverse anatomical variants.
Drugs that improve symptoms in patients with heart failure must also be assessed for their effects on survival. Ibopamine stimulates DA-1 and DA-2 receptors and causes peripheral and renal ...vasodilatation; the drug improves symptoms of heart failure. We assessed the effect of ibopamine on survival in patients with advanced heart failure in a multicentre, randomised placebo-controlled study.
Patients with advanced severe heart failure (New York Heart Association classes III and IV) and evidence of severe left-ventricular disease, who were already receiving optimum treatment for heart failure, were randomly allocated oral ibopamine 100 mg three times daily or placebo. The primary endpoint was all-cause mortality. The study was designed to recruit 2200 patients, and the minimum duration of treatment would be 6 months. We did intention-to-treat and on-treatment analyses; a post-hoc subgroup analysis was also done.
After we had recruited 1906 patients the trial was stopped early, because of an excess of deaths among patients in the ibopamine group. 232 (25%) of 953 patients in the ibopamine group died, compared with 193 (20%) of 953 patients in the placebo group (relative risk 1·26 95% Cl 1·04–1·53, p=0·017). The average length of follow-up was 347 days in the ibopamine group and 363 days in the placebo group. In multivariate analysis, only the use of antiarrhythmic drugs at baseline was a significant independent predictor of increased fatality in ibopamine-treated patients.
Ibopamine seems to increase the risk of death among patients with advanced heart failure who are already receiving optimum therapy, but the reasons for this increase are not clear. Our finding that antiarrhythmic treatment was a significant predictor of increased mortality in ibopamine-treated patients may be important, but exploratory analyses must be interpreted with caution.
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