Search

BackgroundAnalyses of the effect of pre-stroke functional levels on the outcome of endovascular therapy (EVT) have focused on the course of patients with moderate to substantial pre-stroke disability. The effect of complete freedom from pre-existing disability (modified Rankin Scale (mRS) 0) versus predominantly mild pre-existing disability/symptoms (mRS 1–2) has not been well delineated.MethodsThe HERMES meta-analysis pooled data from seven randomized trials that tested the efficacy of EVT. We tested for a multiplicative interaction effect of pre-stroke mRS on the relationship between treatment and outcomes. Ordinal regression was used to assess the association between EVT and 90-day mRS (primary outcome) in the subgroup of patients with pre-stroke mRS 1–2. Multivariable regression modeling was then used to test the effect of mild pre-stroke disability/symptoms on the primary and secondary outcomes (delta-mRS, mRS 0–2/5–6) compared with patients with pre-stroke mRS 0.ResultsWe included 1764 patients, of whom 199 (11.3%) had pre-stroke mRS 1–2. No interaction effect of pre-stroke mRS on the relationship between treatment and outcome was observed. Patients with pre-stroke mRS 1–2 had worse outcomes than those with pre-stroke mRS 0 (adjusted common OR (acOR) 0.53, 95% CI 0.40 to 0.70). Nonetheless, a significant benefit of EVT was observed within the mRS 1–2 subgroup (cOR 2.08, 95% CI 1.22 to 3.55).ConclusionsPatients asymptomatic/without disability prior to onset have better outcomes following EVT than patients with mild disability/symptoms. Patients with pre-stroke mRS 1–2, however, more often achieve good outcomes with EVT compared with conservative management. These findings indicate that mild pre-existing disability/symptoms influence patient prognosis after EVT but do not diminish the EVT treatment effect.

OBJECTIVES: In a cohort of early rheumatoid arthritis (RA) patients, we aimed to determine and characterise fatigue trajectories over 10 years of follow-up and identify predictors of trajectory membership. METHODS: We selected patients fulfilling the 2010 ACR/EULAR criteria for RA included in the ESPOIR cohort. We used a cluster analysis to obtain fatigue (assessed by fatigue visual analogue scale) trajectories over the course of 10 years from enrolment. Chi-square tests or ANOVA were performed to evaluate differences of baseline variables between fatigue trajectories. Using a multinomial logistic regression we were able to identify predictors of trajectory membership. RESULTS: We analysed 598 patients with mean disease duration at enrolment of 26.2±40.9 days. Cluster analysis revealed 3 trajectories: high (18%), moderate (52%) and low fatigue (30%). Compared to patients with moderate or low fatigue trajectory, patients with high fatigue trajectory were predominantly women and reported significantly higher duration and intensity of morning stiffness, HAQ score, tender joints count, levels of pain, number of awakenings due to arthritis, frequency of fibromyalgic RA, levels of physician and patient global assessment, more frequent sleep problems, and increased psychological distress. Female patients with pain, psychological distress and presence of sicca symptoms had a higher risk of being in the high trajectory group. CONCLUSIONS: These findings suggest that levels of fatigue are rather stable over time in each trajectory. Baseline clinical measures and baseline patient-reported measures of functional status better distinguished the three fatigue trajectories. We did not find any differences between trajectories in baseline laboratory measures. Inflammatory activity was not a predictor of being in the high trajectory fatigue group.

Background Analyses of the effect of pre-stroke functional levels on the outcome of endovascular therapy (EVT) have focused on the course of patients with moderate to substantial pre-stroke disability. The effect of complete freedom from pre-existing disability (modified Rankin Scale (mRS) 0) versus predominantly mild pre-existing disability/symptoms (mRS 1-2) has not been well delineated. Methods The HERMES meta-analysis pooled data from seven randomized trials that tested the efficacy of EVT. We tested for a multiplicative interaction effect of pre-stroke mRS on the relationship between treatment and outcomes. Ordinal regression was used to assess the association between EVT and 90-day mRS (primary outcome) in the subgroup of patients with pre-stroke mRS 1-2. Multivariable regression modeling was then used to test the effect of mild pre-stroke disability/symptoms on the primary and secondary outcomes (delta-mRS, mRS 0-2/5-6) compared with patients with pre-stroke mRS 0. Results We included 1764 patients, of whom 199 (11.3%) had pre-stroke mRS 1-2. No interaction effect of pre-stroke mRS on the relationship between treatment and outcome was observed. Patients with pre-stroke mRS 1-2 had worse outcomes than those with pre-stroke mRS 0 (adjusted common OR (acOR) 0.53, 95% CI 0.40 to 0.70). Nonetheless, a significant benefit of EVT was observed within the mRS 1-2 subgroup (cOR 2.08, 95% CI 1.22 to 3.55). Conclusions Patients asymptomatic/without disability prior to onset have better outcomes following EVT than patients with mild disability/symptoms. Patients with pre-stroke mRS 1-2, however, more often achieve good outcomes with EVT compared with conservative management. These findings indicate that mild pre-existing disability/symptoms influence patient prognosis after EVT but do not diminish the EVT treatment effect.

Background and Purpose- Computed tomographic perfusion (CTP) thresholds associated with follow-up brain infarction may differ by time from symptom onset to imaging and reperfusion. We confirm CTP thresholds over time to imaging and reperfusion in patients with acute ischemic stroke from the HERMES collaboration (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials) data. Methods- Patients with occlusion on CT angiography were acutely imaged with CTP. Noncontrast CT and magnetic resonance-diffusion weighted imaging at 24 to 48 hours defined follow-up infarction. Reperfusion was assessed on conventional angiogram. Tmax, cerebral blood flow (CBF), and cerebral blood volume maps were derived from delay-insensitive CTP postprocessing. These parameters were analyzed using receiver operator characteristics to derive optimal thresholds based on time from stroke onset-to-CTP or to reperfusion. ANOVA and linear regression were used to test whether the derived CTP thresholds were different by time. Results- One hundred thirty-seven patients were included. Tmax thresholds of >15.7 s and >15.8 s and absolute CBF thresholds of 0.05). A statistically significant relationship was observed between CTP-to-reperfusion time and the optimal thresholds for Tmax (P

Given parameters $x \notin \mathbb{R}^- \cup \{1\}$ and $\nu$, $\mathrm{Re}(\nu) < 0$, and the space $\mathscr{H}_0$ of entire functions in $\mathbb{C}$ vanishing at $0$, we consider the family of operators $\mathfrak{L} = c_0 \cdot \delta \circ \mathfrak{M}$ with constant $c_0 = \nu(1-\nu)x/(1-x)$, $\delta = z \, \mathrm{d}/\mathrm{d}z$ and integral operator $\mathfrak{M}$ defined by $$ \mathfrak{M}f(z) = \int_0^1 e^{- \frac{z}{x}t^{-\nu}(1-(1-x)t)} \, f \left ( \frac{z}{x} \, t^{-\nu}(1-t) \right ) \, \frac{\mathrm{d}t}{t}, \qquad z \in \mathbb{C}, $$ for all $f \in \mathscr{H}_0$. Inverting $\mathfrak{L}$ or $\mathfrak{M}$ proves equivalent to solve a singular Volterra equation of the first kind. The inversion of operator $\mathfrak{L}$ on $\mathscr{H}_0$ leads us to derive a new class of linear inversion formulas $T = A(x,\nu) \cdot S \Leftrightarrow S = B(x,\nu) \cdot T$ between sequences $S = (S_n)_{n \in \mathbb{N}^*}$ and $T = (T_n)_{n \in \mathbb{N}^*}$, where the infinite lower-triangular matrix $A(x,\nu)$ and its inverse $B(x,\nu)$ involve Hypergeometric polynomials $F(\cdot)$, namely $$ \left\{ \begin{array}{ll} A_{n,k}(x,\nu) = \displaystyle (-1)^k\binom{n}{k}F(k-n,-n\nu;-n;x), B_{n,k}(x,\nu) = \displaystyle (-1)^k\binom{n}{k}F(k-n,k\nu;k;x) \end{array} \right. $$ for $1 \leqslant k \leqslant n$. Functional relations between the ordinary (resp. exponential) generating functions of the related sequences $S$ and $T$ are also given. These relations finally enable us to derive the integral representation $$ \mathfrak{L}^{-1}f(z) = \frac{1-x}{2i\pi x} \, e^{z} \int_{(0+)}^1 \frac{e^{-xtz}}{t(1-t)} \, f \left ( xz \, (-t)^{\nu}(1-t)^{1-\nu} \right ) \, \mathrm{d}t, \quad z \in \mathbb{C}, $$ for the inverse $\mathfrak{L}^{-1}$ of operator $\mathfrak{L}$ on $\mathscr{H}_0$, where the integration contour encircles the point 0., Comment: 29 pages, 2 figures. arXiv admin note: substantial text overlap with arXiv:1904.08283

The reliability of a generic health-related quality of life measure was assessed for subjects with major amputation of one or several limbs. The Nottingham Health Profile was sent a first time to 1011 limb amputees, and a second time to the 542 respondents to the first inquiry. The intraclass correlation coefficient (ICC) between the answers to each survey was highest for the categories of distress caused by pain (ICC = 0.83), emotional reactions (ICC = 0.83) and mobility (ICC = 0.81). It was found satisfactory for energy level (ICC = 0.75), sleep (ICC = 0.75) and social isolation (ICC = 0.64). It is concluded that the NHP is a reliable health related quality of life measure for amputees.

International audience; Patient reported outcomes (PROs) are relevant in rheumatology. Variable accessibility and validity of commonly used PROs are obstacles to homogeneity in evidence synthesis. The objective of this project was to provide a comprehensive library of "validated PROs".A launch meeting with rheumatologists, PROs methodological experts, and patients, was held to define the library's aims and scope, and basic requirements. To feed the library we performed systematic reviews on selected diseases and domains. Relevant information on PROs was collected using standardised data collection forms based on the COSMIN checklist.The EULAR Outcomes Measures Library (OML), whose aims are to provide and to advise on PROs on a user-friendly manner albeit based on scientific grounds, has been launched and made accessible to all. PROs currently included cover any domain and, are generic or specifically target to the following diseases: rheumatoid arthritis, osteoarthritis, spondyloarthritis, low back pain, systemic lupus erythematosus, gout, osteoporosis, juvenile idiopathic arthritis, and fibromyalgia. Up to 236 instruments (106 generic and 130 specific) have been identified, evaluated, and included. The systematic review for SLE, which yielded 10 specific instruments, is presented here as an example. The OML website includes, for each PRO, information on the construct being measured and the extent of validation, recommendations for use, and available versions; it also contains a glossary on common validation terms.The OML is an in progress library led by rheumatologists, related professionals and patients, that will help to better understand and apply PROs in rheumatic and musculoskeletal diseases.

The Rheumatoid and Arthritis Outcome Score (RAOS) was recently developed to evaluate functional disability and quality of life in rheumatoid arthritis (RA) patients suffering from lower limb symptoms. The aims of this study were to cross-culturally adapt the RAOS into French and to assess its psychometric properties, in particular, responsiveness following intra-articular therapy.The French RAOS was developed according to cross-cultural guidelines and was then evaluated in symptomatic RA patients with lower limb joint involvement. The psychometric properties assessed were - feasibility: percentage of missing data and floor and ceiling effects; reliability: intra-class correlation coefficients (ICC, and Bland and Altman representation; internal consistency: Cronbach's alpha; construct validity by correlation with the SF-36 and HAQ (Spearman's rank test); responsiveness to intra-articular corticosteroid injection (hip, knee, hindfoot) using standardised response mean (SRM) and effect size.Sixty patients were included (mean age 50.1±10.5 years). Neither floor nor ceiling effects were observed. Reliability was good with ICC for different RAOS subscales ranging from 0.76 to 0.91. Results for internal consistency (Cronbach's alpha ranging from 0.73 to 0.91) and construct validity were good. The responsiveness was moderate to large with SRMs ranging from 0.75 to 0.87 and effect sizes from 0.77 to 1.75 at two weeks following intra-articular corticosteroid injection.The French version of the RAOS demonstrated good psychometric properties to capture functional disability and quality of life in RA. Moreover, the results suggest that the RAOS could be used as an outcome in trials evaluating single joint intra-articular injections.

To adapt and validate a telephone questionnaire for case detection of rheumatoid arthritis (RA) and spondyloarthropathies (SpA) in the Serbian population.A questionnaire, developed by the French Society of Rheumatology and successfully tested in France, was adapted to the Serbian language using a cross-cultural adaptation process. It was validated in 150 patients: 50 with RA, 50 with SpA and 50 with degenerative rheumatic disorders. They were recruited from Institute of Rheumatology in Belgrade, hospital registry, years 2001 and 2002. The questionnaire validity was assessed in reference to clinical diagnosis and ACR 1987 and ESSG 1991 classification criteria. A logistic regression model was used for RA-control and SpA-control comparison to identify the set of items that best discriminates these groups.Cross-cultural adaptation of the Questionnaire was successfully achieved, verifying its equivalence with the original (semantic, idiomatic, experiential, conceptual). According to the logistic regression, two items selected for RA provided 92.1% agreement when using either clinical diagnosis or ACR classification criteria as a standard. SpA-control comparison included five items providing 96.8% agreement with clinical diagnosis and four items providing 94.1% agreement with ESSG criteria. Results of the present study are similar to those found in the French study.Validation results of the telephone questionnaire, translated and adapted to the Serbian language, confirm that it can be used as a detection tool for RA and SpA cases in the population of Serbia, whose diagnoses would have to be further confirmed.

This study investigated the reliability and the validity of the QUANTAP (QUANTification de l'Activité Physique) interview-administered survey, a new computer-assisted tool designed to determine physical activity over a lifetime.The tool was used to assess lifetime exercise habits in four dimensions (sport at school, leisure sport, occupation, daily activities) in 419 men and women aged 13-90 years. Physical activity indicators (time spent and energy expenditure) were calculated for 20-year periods. The inter-observer and intra-observer reliability of the tool was studied in two subgroups of 30 subjects.Intraclass correlation coefficients for intra-observer and inter-observer reliability varied from 0.56 to 0.96 and from 0.42 to 0.99 respectively according to the dimensions and indicators considered. Energy expenditure was not statistically significantly different from recommended nutritional intake in either males or females. Percent body fat at the time of the survey correlated with leisure sport (particularly in recent periods of practice): age-adjusted correlation coefficients varied from - 0.23 to - 0.45 among males, and from - 0.19 to - 0.31 among females.The results indicate that QUANTAP is reliable and valid to assess lifetime physical activity. It therefore provides a tool with which the long-term effects of physical activity on current health may be studied.

Item does not contain fulltext

Objective To adapt and validate a telephone questionnaire for case detection of rheumatoid arthritis (RA) and spondyloarthropathies (SpA) in the Serbian population. Methods A questionnaire, developed by the French Society of Rheumatology and successfully tested in France, was adapted to the Serbian language using a cross-cultural adaptation process. It was validated in 150 patients: 50 with RA, 50 with SPA and 50 with degenerative rheumatic disorders. They were recruited from Institute of Rheumatology in Belgrade, hospital registry, years 2001 and 2002. The questionnaire validity was assessed in reference to clinical diagnosis and ACR 1987 and ESSG 1991 classification criteria. A logistic regression model was used for RA-control and SpA-control comparison to identify the set of items that best discriminates these groups. Results Cross-cultural adaptation of the Questionnaire was successfully achieved, verifying its equivalence with the original (semantic, idiomatic, experiential, conceptual). According to the logistic regression, two items selected for RA provided 92.1% agreement when using either clinical diagnosis or ACR classification criteria as a standard. SpA-control comparison included five items providing 96.8% agreement with clinical diagnosis and four items providing 94.1% agreement with ESSG criteria. Results of the present studv are similar to those found in the French study. Conclusion Validation results of the telephone questionnaire, translated and adapted to the Serbian language, confirm that it can be used as a detection tool for RA and SpA cases in the population of Serbia, whose diagnoses would have to be further confirmed.

International audience; The present review describes two different applications of the phototherapy. The first one referred as Photodynamic Therapy (PDT) is widely used for pathologically proliferated tissues, including cancer. PDT is based on the combined action of three parameters: photosensitizer, light and oxygen, resulting in the production of toxic reactive oxygen species. To improve the selectivity of phosensitizers for pathological tissues the liposomal photosensitizers formulations have been proposed favoring tumor targeting. The comprehension of the mechanisms that govern the drug release processes of photosensitizers in liposomal nanostructures and as such their pharmacokinetics behavior is essential and is addressed in the present review. Another facet of nanoparticles-based photoinduced therapy is related to tissue regeneration. Complex mechanisms of photoinduced wound healing and repair will be considered, including the role of different cell types, growth factors and antimicrobial action. In conclusion, PDT offers two contrasting strategies either to eradicate pathological tissues or to stimulate tissue repair. In fine, consideration of all parameters involved in this kind of phototherapy is required to obtain a desired effect and optimize clinical protocols.

International audience; Context: The OFSEP registry in multiple sclerosis (MS) recently proposed a high-definition (HD) cohort to better appreciate the causal factors of disease progression and develop reliable predictive tools to help in medical decision making and informing patients at different key moments in the disease course.Objectives: To describe the characteristics of the first patients included in the HD cohort and to analyse their cross-sectional relationship with quality of life (QoL) measures.Methods: MS patients are followed annually. Data collection includes OFSEP core minimal clinical data, MFSC, brain MRI, comorbidities, serum biomarkers and patient-reported outcomes including QoL. Inclusions in the HD cohort started in July 2018. Patients were described according to demographic, clinical and therapeutic characteristics at inclusion. Several QoL indicators were available: the visual analogue scale (VAS) of the EQ5D-5L, the physical (PCS) and mental (MCS) component summary scores of the SF12, and the summary index of the MuSiQoL. Associations between patients’ characteristics and QoL indicators were analysed with multiple linear regression (p< 0.05 was considered as significant).Results: In March 2019, 621 patients were included, mainly women (73%), with an age at inclusion of 43±11 years and disease duration of 12±9 years. Disease course was relapsing-remitting (80%), secondary (12%) and primary progressive (8%). Majority of patients had a low disability (EDSS [0-2.5], 57%; [3-3.5], 12%; [4-5.5], 18.2%; [6-7], 13%). Twenty two percent were untreated; others were mainly treated with natalizumab (22%), fingolimod (14%) and rituximab (10%). In multivariate analysis, VAS was significantly lower in patients with progressive course and high levels of EDSS. The same correlations were observed for the PCS, which was additionally higher in first line treated patients. Regarding the MusiQoL, its level was significantly lower in patients with high levels of EDSS. In contrast, MCS was higher for EDSS [0-2.5] and lower for [4-5.5].Discussion: The first patients included in the HD cohort had a low disability and were mostly treated with second line drugs. A low QoL was associated to higher EDSS but not to disease activity; clinical course and treatment were associated with some scales but not for others. The relationship observed between QoL and disability validates the usefulness of the QoL collection of data in the perspective of a patient-centred research program.

Cardiac failure has a big impact on the daily life of patients and this can be evaluated using quality of life questionnaires. The aim of this study was to translate and adapt for the French population and test the validity of two quality of life self-administered-questionnaires: the Duke health Profile, the Minnesota Quality of Life Questionnaire in Cardiac Failure and one function capacity questionnaire, the Goldman Specific Activity Scale. The questionnaires were translated and retranslated then submitted to a committee of experts: the final version was presented to 30 patients. The study of the quantitative properties of the three instruments was performed on a sample of 74 patients with cardiac failure to assess their validity and 26 stable patients after cardiac transplantation to test reproducibility. The results of this study show that these three instruments are valid and reproducible and are comparable to the original documents: Cronbach's Alpha ranging from 0.54 to 0.78 for the Duke, except for the social dimension, and from 0.73 to 0.93 for the Minnesota, except for its incapacity dimension, intraclass correlation coefficient0.6 in all dimensions. The validity of convergence with LVEF and the NYHA measured during hospitalisation for decompensation was poor, except for the Goldman. The three instruments provided coherent information. The authors conclude that a structured method allows transcultural adaptation of instruments of evaluation of quality of life, the French version having comparable properties to the original documents: they may be used for clinical research.

A good sensitizer for photodynamic therapy (PDT) should be a very selective reagent, which should fastly eliminate from healthy tissues. Furthermore it should have a strong absorption in the red light and good energy transfer properties to molecular oxygen to produce singlet oxygen. All these specifications imply that many second generation photosensitizers (porphyrins, chlorins, bacteriochlorins...) have been modified in order to improve their properties, but however, few have received the approval by regulatory authorities. One way to increase the selectivity of a photosensitizer is coupling it to a vector. Carbohydrate-bound porphyrins were found to be of great interest because of the specific affinity of particular carbohydrates for some tumour cells, the increasing of plasmatic life time and solubility. In this study, we report the synthesis and the photophysical properties (absorption, fluorescence, singlet oxygen formation) of new glycosylated porphyrins. Then, in vitro photocytotoxic properties were evaluated on the human colon adenocarcinoma cell line HT29.

The need to evaluate or quantify an individual's physical activity often raises the problems of choosing the instrument which most adequately meets the requirements of the study. This article offers a presentation of various questionnaires available in the literature. It proposes a table intended to characterize these questionnaires as well as a summary of validation steps. These tools allow rapid comparisons between questionnaires and are helpful in guiding the user's choice of a well adapted questionnaire.

In multiple sclerosis, treatment start or switch is prompted by evidence of disease activity. Whilst immunomodulatory therapies reduce disease activity, the time required to attain maximal effect is unclear. In this study we aimed to develop a method that allows identification of the time to manifest fully and clinically the effect of multiple sclerosis treatments ('therapeutic lag') on clinical disease activity represented by relapses and progression-of-disability events. Data from two multiple sclerosis registries, MSBase (multinational) and OFSEP (French), were used. Patients diagnosed with multiple sclerosis, minimum 1-year exposure to treatment, minimum 3-year pretreatment follow-up and yearly review were included in the analysis. For analysis of disability progression, all events in the subsequent 5-year period were included. Density curves, representing incidence of relapses and 6-month confirmed progression events, were separately constructed for each sufficiently represented therapy. Monte Carlo simulations were performed to identify the first local minimum of the first derivative after treatment start; this point represented the point of stabilization of treatment effect, after the maximum treatment effect was observed. The method was developed in a discovery cohort (MSBase), and externally validated in a separate, non-overlapping cohort (OFSEP). A merged MSBase-OFSEP cohort was used for all subsequent analyses. Annualized relapse rates were compared in the time before treatment start and after the stabilization of treatment effect following commencement of each therapy. We identified 11 180 eligible treatment epochs for analysis of relapses and 4088 treatment epochs for disability progression. External validation was performed in four therapies, with no significant difference in the bootstrapped mean differences in therapeutic lag duration between registries. The duration of therapeutic lag for relapses was calculated for 10 therapies and ranged between 12 and 30 weeks. The duration of therapeutic lag for disability progression was calculated for seven therapies and ranged between 30 and 70 weeks. Significant differences in the pre- versus post-treatment annualized relapse rate were present for all therapies apart from intramuscular interferon beta-1a. In conclusion we have developed, and externally validated, a method to objectively quantify the duration of therapeutic lag on relapses and disability progression in different therapies in patients more than 3 years from multiple sclerosis onset. Objectively defined periods of expected therapeutic lag allows insights into the evaluation of treatment response in randomized clinical trials and may guide clinical decision-making in patients who experience early on-treatment disease activity. This method will subsequently be applied in studies that evaluate the effect of patient and disease characteristics on therapeutic lag. This study was supported by the EDMUS Foundation, Biogen and NHMRC (1140766, 1129189, 1157717). I.R. is supported by a MSIF-ARSEP McDonald fellowship grant and a Melbourne Research Scholarship. The MSBase Foundation is a not-for-profit organization that receives support from Biogen, Novartis, Merck, Roche, Teva and Sanofi Genzyme. The Observatoire Francais de la Sclerose en Plaques (OFSEP) is supported by a grant provided by the French State and handled by the 'Agence Nationale de la Recherche,' within the framework of the 'Investments for the Future' program, under the reference ANR-10-COHO-002, by the Eugene Devic EDMUS Foundation against multiple sclerosis and by the ARSEP Foundation. The study was conducted separately and apart from the guidance of the sponsors. Kalincik, T (corresponding author), Univ Melbourne, Dept Med, CORe, 300 Grattan St, Melbourne, Vic 3050, Australia. tomas.kalincik@unimelb.edu.au