Long-term outcome of children treated with rituximab for idiopathic nephrotic syndrome

Background

Rituximab (RTX) has recently showed promising results in the treatment of steroid-dependent idiopathic nephrotic syndrome (SDNS).

Methods

This was a retrospective multicenter study of 18 children treated with RTX for SDNS, with a mean follow-up of 3.2 years. RTX was introduced because of side effects or relapses during therapy with immunosuppressive agents. The children received one to four infusions of RTX during the first course of treatment, and subsequent infusions were given due to CD19-cell recovery (CD19?>1 %; 54 % of children) or relapse (41 %), as well as systematically (5 %).

Results

Treatment with RTX maintained sustained remission without relapse in 22 % of patients and increased the duration of remission in all other patients. The time between two successive relapses was 9 months in the absence of re-treatment and 24.5 months when infusions were performed at the time of CD19-cell recovery. At the last follow-up, 44.5 % of patients were free of oral drug therapy. Of those still receiving oral drugs, all doses had been decreased. No serious adverse events occurred.

Conclusion

The results of this retrospective study confirm the efficacy and very good safety of RTX in the treatment of SDNS. The optimal therapeutic protocol seems to be a repeated single infusion at the time of CD19-cell recovery.     

Efetividade da infiltração intra-articular guiada por imagem: comparação entre fluoroscopia e ultrassom

ObjectiveCompare the effectiveness of ultrasound and fluoroscopy to guide intra-articular injections (IAI) in selected cases.Material and methodsA prospective study in our outpatient clinics at the Rheumatology Division at Universidade Federal de São Paulo (UNIFESP), Brazil, was conducted to compare the short-term (4 weeks) effectiveness of ultrasound and fluoroscopy-guided IAI in patients with rheumatic diseases. Inclusion criteria were: adults with refractory synovitis undergo- ing IAI with glucocorticoid. All patients had IAI performed with triamcinolone hexaceton- ide (20 mg/ml) with varying doses according to the joint injected.ResultsA total of 71 rheumatic patients were evaluated (52 women, 44 whites). Mean age was 51.9 ± 13 years and 47 of them (66.2%) were on regular DMARD use. Analysis of the whole sample (71 patients) and hip sub-analysis (23 patients) showed that significant im- provement was observed for both groups in terms of pain (P < 0.001). Global analysis also demonstrated better outcomes for patients in the FCG in terms of joint flexion (P < 0.001) and percentage change in joint flexion as compared to the USG. Likert scale score analyses demonstrated better results for the patients in the USG as compared to the FCG at the end of the study (P < 0.05). No statistically significant difference between groups was observed for any other study variable.Discussion and conclusionImaging-guided IAI improves regional pain in patients with vari- ous types of synovitis in the short term. For the vast majority of variables, no significant difference in terms of effectiveness was observed between fluoroscopy and ultrasound- guided IAI.     

Real frequency of ordinary and atypical sub-trochanteric and diaphyseal fractures in France based on X-rays and medical file analysis

PurposeAtypical sub-trochanteric and femoral shaft fractures have been reported in patients treated with bisphosphonates. Their incidence has been determined from registered data analysis using international codes. Therefore, the aim of our study was to estimate the real frequency of typical and atypical sub-trochanteric or diaphyseal fractures, based on radiological and clinical data compared to registered data.MethodsIn the registers of three large French University Hospitals, patients identified with International Classification of Diseases, 10th Revision diagnosis codes for sub-trochanteric or diaphyseal fracture were selected. Frequencies of ordinary and atypical fractures were calculated after both registered data, radiological and clinical files analysis.ResultsAmong the 4592 patients hospitalized for a femoral fracture over 5 years, 574 were identified to have had a sub-trochanteric or femoral shaft fracture. 47.7% of the sub-trochanteric and femoral shaft fractures were misclassified, predominantly in the sub-trochanteric fractures subset. 12 patients had an atypical fracture (4% of the sub-trochanteric and femoral shaft fractures) and 11 fractures presented radiological features of atypical fractures, whereas clinical files analysis revealed they were pathological or traumatic fractures.ConclusionAtypical fractures frequency is very low. Because of their low frequency and the unreliability of registered databases, the risk of atypical fractures is very difficult to estimate retrospectively. A prospective study is needed to clarify the risk factors associated with these fractures.     

Risk of recurrent venous thromboembolism among young women after a first event while exposed to combined oral contraception versus not exposed to: A cohort study

The risk of recurrent venous thromboembolism (VTE) in young women after a first oestrogen contraception associated VTE episode is unknown. This uncertainty has an impact on the decision whether to stop anticoagulant treatment. Our objective was to assess the risk of recurrent VTE in women after a first VTE episode on oestrogen contraception. This was a prospective cohort study in which we consecutively enrolled between 1992 and 2011 all women under 50 years with a first objectively confirmed VTE. The incidence of recurrent VTE during follow-up after stopping anticoagulation was compared between women users and non-users of combined oral contraception (COC) at the time of index VTE. Of the 241 women aged 50 or younger seen for a first VTE and followed-up after stopping anticoagulation, there were 180 COC-users and 61 non-users. Median duration of follow-up off-anticoagulants was 66 months (interquartile range: 33–103). There were 14 recurrences in COC-users and 5 cases in non-users. No significant association was found between exposure to COC and the incidence of recurrent VTE after adjustment for age or after restricting the analysis to major unprovoked VTE: incidence rate of recurrence 17.9/1,000/year (95% CI: 9.6-33.2) in women with COC as compared with 17.6/1,000/year (95% CI: 6.6-47) with an incidence ratio of 0.7 (95% CI: 0.2-2.4, p = 0.59). The risk of recurrent VTE is low in young women after a first VTE. However, this risk is not significantly lower in women after a first VTE while exposed to combined oral contraception.     

Drug trajectories among youth undergoing treatment: The influence of psychological problems and delinquency

Previous research has documented associations of addiction with delinquency and psychological problems. However, few studies have evaluated their influence on adolescent's drug use trajectories. The current study aims to examine the influence of these factors on the recovery trajectories of 199 youths aged 15.6 years on average admitted to inpatient and outpatient addiction treatment centers, followed up three and six months later. Results indicate that youth who show higher severity of drug abuse exhibit greater improvement than youth with a lower severity of drug abuse at the onset of treatment. Although psychological problems were associated with baseline drug use, they did not influence drug use trajectory over time. Only delinquency influenced the recovery trajectories of these youth. Results suggest that a high level of delinquency can have a significant effect on the drug recovery process of adolescents and that interventions should attempt to reduce both drug use and delinquency.     

A comparison of client and therapist goals for people with aphasia: A qualitative exploratory study

Background: A considerable body of literature attests to the efficacy of client and therapist collaborative goal setting to achieving optimal rehabilitation outcomes. Collaborative goal setting and shared decision making relies on good communication, thus potentially disadvantaging people with aphasia.

Aims: This study aims to identify the similarities and differences between client goals and therapist goals in rehabilitation for people with aphasia and to explore reasons why any differences occur.

Methods & Procedures: Three speech-language pathologists and four people with aphasia participated in in-depth semi-structured interviews to identify rehabilitation goals. All the interviews were transcribed and analysed using qualitative content analysis.

Outcomes & Results: Results indicated both matching and mismatching of goals between the clients and the speech-language pathologists. Matched goals tended to focus on communication outcomes. Mismatched goals were those associated with the client's desire to return to previously valued activities. Reasons for the mismatching included: impaired communication made collaboration on goal setting difficult, the service-delivery approach, the goal was perceived to be outside the speech-language pathologist's scope of practice, and the goal was not considered to be appropriate within the confines of the rehabilitative situation.

Conclusions: This study highlights the need for speech-language pathologists to understand their clients' goals and how these can be incorporated into rehabilitation. A re-examination of some professional beliefs was highlighted. Future research may lead to educational resources that enable better collaborative goal setting between therapist and client so that outcomes of rehabilitation are optimised.     

Evaluation of the ability of Streptococcus agalactiae strains isolated from genital and neonatal specimens to bind to human fibrinogen and correlation with characteristics of the fbsA and fbsB genes

The ability of 111 Streptococcus agalactiae strains to bind to human fibrinogen was quantified. We correlated the percentages of bacteria that bound to immobilized fibrinogen with fibrinogen-binding (fbs) gene characteristics of strains and with clinical origin, serotypes, and phylogenetic positions of strains. Percentages varied from 0.4 to 29.9%. Fifty-five strains (49.5%) had the fbsB gene sensu stricto described by Gutekunst et al. (Infect. Immun., 72:3495-3504, 2004), allowing adhesion to human fibrinogen, and all of the other strains had an fgag variant gene. Ninety strains (81.1%) had a fbsA gene and 55 of them also had the fbsB gene. The other 21 strains (18.9%) had a truncated form of fbsA without the fbsB gene sensu stricto. The numbers of 48-nucleotide repeat sequences (rs) in the fbsA gene varied from 2 to 26. The population of strains with the highest ability to bind to human fibrinogen significantly more frequently had the fbsB gene sensu stricto and 4 to 7 rs in the fbsA gene (P < 0.05). However, the single strain that carried the highest number of rs (26 rs) in the fbsA gene showed high fibrinogen-binding activity (24.3%). Strains exhibiting significantly higher levels of binding to human fibrinogen belonged to a phylogenetic group of strains associated with neonatal meningitis, currently known as the ST-17 clone, that is mostly composed of serotype III strains. These findings indicate that S. agalactiae strains possess a wide variety of fbs gene content that markedly influences the ability of strains to bind to human fibrinogen. Variations in the configuration and the expression of the Fbs proteins may therefore partly explain the variability of virulence in S. agalactiae species.     

Recirculating CD4 memory T cells mount rapid secondary responses without major contributions from follicular CD4 effectors and B cells

For weeks after primary immunization with thymus-dependent antigens the responding lymph nodes contain effector CD4 T cells in T zones and germinal centers as well as recirculating memory T cells. Conversely, remote nodes, not exposed to antigen, only receive recirculating memory cells. We assessed whether lymph nodes with follicular effector CD4 T cells in addition to recirculating memory CD4 T cells mount a more rapid secondary response than nodes that only contain recirculating memory cells. Also, the extent to which T cell frequency governs accelerated CD4 T cell recall responses was tested. For this, secondary antibody responses to a superantigen, where the frequency of responding T cells is not increased at the time of challenge, were compared with those to conventional protein antigens. With both types of antigens similar accelerated responses were elicited in the node draining the site of primary immunization and in the contralateral node, not previously exposed to antigen. Thus recirculating memory cells are fully capable of mounting accelerated secondary responses, without the assistance of CD4 effector T cells, and accelerated memory responses are not solely dependent on higher T cell frequencies. Accelerated memory CD4 T cell responses were also seen in B cell-deficient mice.