Nusinersen treatment in adults with severe spinal muscular atrophy: A real-life retrospective observational cohort study.

BACKGROUND AND OBJECTIVES: Spinal muscular atrophy (SMA) is a progressive neurodegenerative disease due to homozygous loss-of-function of the survival motor neuron gene SMN1 with absence of the functional SMN protein. Nusinersen, a costly intrathecally administered drug approved in 2017 in Europe, induces alternative splicing of the SMN2 gene, which then produces functional SMN protein, whose amount generally increases with the number of SMN2 gene copies. METHODS: We retrospectively collected data from consecutive wheelchair-bound adults with SMA managed at a single center in 2018-2020. The following were collected at each injection, on days 1, 14, 28, 63, 183, and 303: 32-item Motor Function Measurement (MFM) total score and D2 and D3 subscores; the Canadian Occupational Performance Measure (COPM) performance and satisfaction scores; and lung function tests. The patients were divided into two groups based on whether their MFM total score was

Text input speed in persons with cervical spinal cord injury.

STUDY DESIGN: This is a prospective clinical study. OBJECTIVES: The objectives of this study were to determine text input speed (TIS) in persons with cervical spinal cord injury (SCI) and to study the influence of personal characteristics and type of computer access device on TIS. SETTING: This study was conducted in the Rehabilitation Department, Garches, France. METHODS: People with cervical SCI were included if their level of injury was between C4 and C8 Asia A or B, and if they were computer users. In addition, able-bodied people were recruited from the hospital staff. Each participant underwent a single evaluation using their usual computer access devices. TIS was evaluated during a 10- min copying task. The relationship between the characteristics of participants with cervical SCI, type of computer access device and TIS were analyzed using a Scheirer-Ray-Hare test (nonparametric test similar to a two-way analysis of variance). RESULTS: Thirty-five participants with cervical SCI and 21 able-bodied people were included. Median TIS of participants with cervical SCI was 11 (6; 14) words per minute (w.p.m.) and of able-bodied participants was 19 (14; 24) w.p.m. (P=0.001). Median TIS of participants with lesions at or above C5 was 12 (4; 13) w.p.m. and of those with lesions below C5 was 10 (9; 18) w.p.m. (P=0.38) [corrected]. The Scheirer-Ray-Hare test showed that only the type of computer access device significantly influenced TIS. Surprisingly, none of the person's characteristics, including the level of cervical lesion, affected TIS. CONCLUSION: This is the first study to analyze TIS in a group of participants with cervical SCI. The results showed that only the type of computer access device influenced TIS.

Value of TENS for relief of chronic low back pain with or without radicular pain.

OBJECTIVES: To evaluate the efficacy of transcutaneous electrical neurostimulation (TENS) in patients with chronic low back pain (LBP). DESIGN: Prospective, randomized, multicentre, single-blind study. SETTING: Twenty-one French pain centres. PARTICIPANTS: Two hundred thirty-six consecutive adult patients consulting for chronic LBP, with or without radicular pain (mean age ± standard deviation: 53 ± 13 years; range: 28-86 years). INTERVENTION: Patients were randomly assigned to receive either active (n = 117) or sham (n = 119) TENS in four 1-h daily treatment sessions for 3 months. MAIN OUTCOME MEASURES: The primary outcome measured was improvement of functional status at 6 weeks (Roland-Morris Disability Questionnaire). Secondary outcome measures were improvement of functional status at 3 months, pain relief (weekly visual analogue scale assessments), positive functional repercussions of pain levels on quality of life, a diminution of the use of analgesic and anti-inflammatory medication, satisfaction with the overall treatment strategy and compliance. RESULTS: Functional status did not differ between the groups, whether at 6 weeks or 3 months (p = 0.351 at 6 weeks). A significant improvement between the first and last visual analogue scale assessments was observed in patients with either lumbar pain alone or lumbar and radicular pain treated with active TENS. Other outcome measures did not differ significantly between the two groups. CONCLUSION: There was no functional benefit of TENS in the treatment of patients with chronic LBP.

Risk of tuberculosis is higher with anti-tumor necrosis factor monoclonal antibody therapy than with soluble tumor necrosis factor receptor therapy: The three-year prospective French Research Axed on Tolerance of Biotherapies registry.

OBJECTIVE: Tuberculosis (TB) is associated with anti-tumor necrosis factor (anti-TNF) monoclonal antibody (mAb) therapy, but whether this association is drug-specific remains a concern. Our objective was to describe cases of TB associated with anti-TNF mAb therapy, identify risk factors, and estimate the incidence. METHODS: We conducted an incidence study and a case-control analysis to investigate the risk of newly diagnosed TB associated with the use of anti-TNF agents. As part of the French Research Axed on Tolerance of Biotherapies (RATIO) registry, for 3 years we collected cases of TB among French patients receiving anti-TNF mAb therapy for any indication; for each case, 2 patients treated with anti-TNF agents served as control subjects. RESULTS: We collected 69 cases of TB in patients treated for rheumatoid arthritis (n = 40), spondylarthritides (n = 18), inflammatory colitis (n = 9), psoriasis (n = 1) and Behçet's disease (n = 1) with infliximab (n = 36), adalimumab (n = 28), and etanercept (n = 5). None of the patients had received correct chemoprophylactic treatment. The sex- and age-adjusted incidence rate of TB was 116.7 per 100,000 patient-years. The standardized incidence ratio (SIR) was 12.2 (95% confidence interval [95% CI] 9.7-15.5) and was higher for therapy with infliximab and adalimumab than for therapy with etanercept (SIR 18.6 [95% CI 13.4-25.8] and SIR 29.3 [95% CI 20.3-42.4] versus SIR 1.8 [95% CI 0.7-4.3], respectively). In the case-control analysis, exposure to infliximab or adalimumab versus etanercept was an independent risk factor for TB (odds ratio [OR] 13.3 [95% CI 2.6-69.0] and OR 17.1 [95% CI 3.6-80.6], respectively). Other risk factors were age, the first year of anti-TNF mAb treatment, and being born in an endemic area. CONCLUSION: The risk of TB is higher for patients receiving anti-TNF mAb therapy than for those receiving soluble TNF receptor therapy. The increased risk with early anti-TNF treatment and the absence of correct chemoprophylactic treatment favor the reactivation of latent TB.

Diagnostic and prognostic values of anti glucose-6-phosphate isomerase antibodies in community-recruited patients with very early arthritis.

The objective of this study was to determine the diagnostic and prognostic values of antiglucose-6-phosphate isomerase (GPI) antibodies in patients with very early arthritis. Anti-GPI antibodies were measured by ELISA using purified GPI from rabbit muscle in: (i) 383 sera from healthy blood donors (n = 120), well-established rheumatoid arthritis (RA) (n = 99) and non-RA differentiated arthritis (NRADA) (n = 164) patients; (ii) 195 sera obtained from community-recruited patients with very early inflammatory arthritis (VErA cohort) that were studied for 1 year and classified as having RA (n = 116), NRADA (n = 41), and undifferentiated arthritis (UA) (n = 38) after the follow-up period. The criterion for severity was the progression of radiographic damage. Prevalence of anti-GPI antibodies was significantly higher in well-established RA patients (45.4%) compared to healthy subjects (2.5%). Anti-GPI antibodies were also present in sera from NRADA: systemic lupus erythematosus 53%, polymyositis 45.4%, adult-onset Still's disease 44%, systemic sclerosis 42.8%, spondylarthropathies 25% and primary Sjögren's syndrome 5.8%. No significant association was found between the presence of anti-GPI antibodies and the 3 diagnostic groups from the VErA cohort. No correlation was observed between anti-GPI and autoantibodies usually associated with RA. Anti-GPI antibodies were not predictive of radiological progression in patients with very early arthritis. Thus, anti-GPI antibodies are not useful for discriminating RA from non-RA rheumatic diseases and do not constitute a predictive factor of structural damage.

Rheumatoid factor is the strongest predictor of radiological progression of rheumatoid arthritis in a three-year prospective study in community-recruited patients.

OBJECTIVE: To evaluate the predictive value of clinical, biological and radiological parameters for the prognosis of rheumatoid arthritis (RA) in a community-recruited cohort. METHODS: Ninety-one patients (mean age 49 yr, female/male ratio 2.9) with RA of limited duration (median 2 yr), 80% recruited from the community, were prospectively enrolled in 1996 (T1) and followed until 1999 (T2). Data collected at T1 were demographic characteristics, Ritchie articular index (RAI), extra-articular manifestations, Health Assessment Questionnaire (HAQ) score, C-reactive protein (CRP) and autoantibodies (autoAbs) [rheumatoid factors (RF), detected by latex fixation test and ELISA (IgM, IgA and IgG isotypes), anti-filaggrin, detected by immunofluorescence (anti-keratin antibodies, AKA; anti-perinuclear factor antibodies, APF) and ELISA (anti-citrullinated rat filaggrin antibodies, ACRFA), anti-Sa, anti-calpastatin recognizing the 27 C-terminal fragment (ACAST-C27) and domain I (ACAST-DI), anti-cardiolipin (ACL), antineutrophil cytoplasmic antibodies (ANCA), anti-annexin V (aANX V) and anti-Ro]. Hands were radiographed at T1 and T2, and read using the Sharp method as modified by van der Heijde. The main assessment criterion was progression of radiologically detected damage between T1 and T2. RESULTS: At T1, RA activity was mild (RAI 11/78; mean CRP 14 mg/ml), with minor functional disability (HAQ 0.8/3) and mild X-ray destruction (mean total Sharp score 9.2/280). At T1, 96% of the patients were on treatment (prednisone 72%, DMARDs 95%). The latex test detected autoAb in 46% of patients, RF-IgM was detected in 51%, RF-IgA in 36%, RF-IgG in 32%, AKA in 33%, APF in 45%, ACRFA in 45%, ACAST-C27 in 14%, ACAST-DI in 5%, anti-Sa in 22%, ACL in 3%, ANCA in 28%, aANX V in 9% and anti-Ro in 2%. At T2, the mean total Sharp score was 22.9. According to univariate analysis, T1 parameters associated with the independent variable were RAI, HAQ, CRP, latex test positivity and T1 Sharp scores. Multivariate analysis retained only latex test positivity and, to a lesser degree, joint-space narrowing score as independent predictors of radiological progression. CONCLUSION: RF is the main factor that can predict radiological progression in community cases of RA of limited duration.

[Adults with sickle cell anemia in Senegal. Clinical study of 40 homozygote subjects]. / L'adulte drépanocytaire au Sénégal. Etude clinique de 40 sujets homozygotes.

While the well-documented life expectancy of patients with homozygous sickle cell anemia (SS) is 40 years in industrialized countries, this question remains unanswered in black Africa. The purpose of this prospective study was to establish the clinical phenotype for Senegal. A severity score based on 12 clinical, laboratory, radiological, and prognostic findings was calculated and correlated with age and hemoglobin F level. A total of 40 SS homozygotes over 15 years of age (mean age: 25 years) were hospitalized between January 1996 and January 1998 at the Principal Hospital in Dakar. The most common events requiring hospitalization were vasoocclusive phenomena (n = 26) but the incidence of these complications declined significantly with age (p < 0.05). The mean hemoglobin level was 4.4 mmol/l and the mean hemoglobin F level was 6.2 p. 100. The incidence of visceral involvement was low (lithiasic vesicules in 17 cases, necrosis of the head of the femur in 7, and abnormal cardiac ultrasound findings in 10). Only one patient died during the study. No correlation was found between severity score and either age or hemoglobin F level. These findings confirm that the phenotype is less severe in Senegal. However they also show that organ damage is common by the time that patients reach adulthood and thus underline the need for prevention and education to improve survival of SS homozygotes in Senegal.