Clinical and instrumental evaluation of Botulinum Toxin type A safety profile in post stroke spasticity rehabilitation treatment

Post stroke spasticity (PSS) occurs approximately in 30% of stroke survivors. Spasticity varies from a subtle neurological sign to a gross increase in tone causing immobility of joints. PSS is associated with several complications, increasing care needs and utilisation of healthcare resources. Botulinum toxin type A (BoNT-A) has been considered as an effective and safe treatment for focal spasticity in stroke survivors, with low prevalence of complications, reversibility of effect, and efficacy in reducing spastic hypertonia. Recent studies estimated that a significant percentage of patients affected by PSS could benefit from higher doses than those permitted by current country directives. However, at present time, there is no general consensus on the maximum dose of BoNT-A in terms of safety and clinical interchangeability among the three commercially approved products (abobotulinumtoxinA, onabotulinumtoxinA, incobotulinumtoxinA). In light of these considerations, the aim of this thesis is to investigate the safety profile of BoNT-A high doses in the treatment of post stroke spasticity. In our research activity we investigated the clinical effect of this treatment in severely affected patients, focusing on both clinical and instrumental assessment of systemic effects of BoNT-A

An accelerated buoyancy adhesion assay combined with 3-D morphometric analysis for assessing osteoblast adhesion on microgrooved substrata.

An accelerated negative buoyancy method has been developed to assess cell adhesion strength. This method has been used in conjunction with 3-D morphometric analysis to understand the effects of surface topology on cell response. Aligned micro-grooved surface topographies (with a range of groove depths) were produced on stainless steel 316L substrates by laser ablation. An investigation was carried out on the effect of the micro-grooved surface topography on cell adhesion strength, cell and nucleus volumes, cell phenotypic expression and attachment patterns. Increased hydrophobicity and anisotropic wettability was observed on surfaces with deeper grooves. A reduction was noted in cell volume, projected areas and adhesion sites for deeper grooves, linked to lower cell proliferation and differentiation rates and also to reduced adhesion strength. The results suggest that the centrifugation assay combined with three-dimensional cell morphometric analysis has considerable potential for obtaining improved understanding of the cell/substrate interface.Financial support for this work has been provided by the EPSRC (grant GR/R95364/01) and by the ERC (grant No. 240446). The authors are grateful to Dr. Tim Nunney, of Thermo-Fisher Scientific, for carrying out the XPS measurements.This is the final version of the article. It first appeared from Elsevier via https://doi.org/ /10.1016/j.jmbbm.2015.12.03

Association between pain and sexual health in older people: results from the English Longitudinal Study of Ageing

There is little information on the impact of pain on sexual health in later life. The aim of this analysis was to determine the association between self-reported pain and sexual health in older men and women. Data were collected for the nationally representative English Longitudinal Study of Ageing. Community-dwelling adults aged 50 years and older completed the Sexual Relationships and Activities questionnaire in wave 6 (2012/2013). Participants were asked (waves 1 to 6 [2002- 2013]) if they were "often troubled with pain" and, how severe was their pain; mild, moderate or severe. The association between pain and sexual health was assessed using logistic regression. Analyses were stratified by gender, with adjustments made for age followed by adjustments for health and lifestyle factors, depressive symptoms and socioeconomic status. Of the 3,916 participants who reported having sexual activity in the past year, 28% of women and 23% of men reported experiencing moderate or severe pain often at wave 6. After adjusting for age, compared to men experiencing no pain, men with moderate or severe pain reported less frequent intercourse and masturbation, more erectile difficulties, and more concerns about their sexual health. After age adjustment there were no associations between pain severity and sexual health among women. Of the 1,872 participants with a cumulative pain score, there were significant associations between reporting pain and concerns about sexual health in both men and women. Pain was associated with impairment in sexual health in men and women though the effect was more marked in men

The efficacy of intra-articular steroids in hip osteoarthritis: a systematic review

© 2016 Osteoarthritis Research Society International Objective International guidelines recommend intra-articular steroid injections (IASIs) in the management of hip osteoarthritis (OA), though these recommendations are extrapolated primarily from studies of knee OA. The aim of this systematic review was to assess the efficacy of IASI on pain in hip OA. Methods MEDLINE, EMBASE, AMED, CINAHL Plus, Web of Science and the Cochrane Central Register of Controlled Trials were searched to May 2015. Randomised controlled trials (RCTs) assessing the efficacy of hip IASI on pain were included. Pre-specified data was extracted using a standardised form. Quality was assessed using the Jadad score. Results Five trials met the inclusion criteria. All had a small number of participants (≤101). All studies reported some reduction in pain at 3–4 weeks post-injection compared to control. Based on data from individual trials the treatment effect size was large at 1 week post-injection but declined thereafter. A significant (moderate effect size) reduction in pain was reported in two trials up to 8 weeks following IASI. Pooled results of two trials (n = 90) showed an increased likelihood of meeting the Outcome measures in Rheumatology Clinical Trials (OMERACT)–Osteoarthritis Research Society International (OARSI) response criteria at 8 weeks post-IASI, odds ratio 7.8 (95% confidence interval (CI): 2.7–22.8). The number needed to treat to achieve one OMERACT–OARSI responder at 8 weeks post-injection was 2.4 (95% CI: 1.7–4.2). Hip IASI appear to be generally well tolerated. Conclusions Hip IASI may be efficacious in short-term pain reduction in those with hip OA though the quality of the evidence was relatively poor. Further large, methodologically rigorous trials are required to verify whether intra-articular corticosteroids are beneficial and for how long

Assessment of bone marrow oedema-like lesions using MRI in patellofemoral knee osteoarthritis: comparison of different MRI pulse sequences

Objective: To compare bone marrow oedema-like lesion (BML) volume in subjects with symptomatic patellofemoral (PF) knee osteoarthritis (OA) using four different MRI sequences and to determine reliability of BML volume assessment using these sequences and their correlation with pain. Methods: 76 males and females (mean age 55.8 years) with symptomatic patellofemoral knee OA had 1.5 T MRI scans. PD fat suppressed (FS), STIR, contrast-enhanced (CE) T1W FS, and 3D T1W fast field echo (FFE) sequences were obtained. All sequences were assessed by one reader, including repeat assessment of 15 knees using manual segmentation and the measurements were compared. We used random-effects panel linear regression to look for differences in the log-transformed BML volume (due to positive skew in the BML volume distribution) between sequences and to determine associations between BML volumes and knee pain. Results: 58 subjects had PF BMLs present on at least one sequence. Median BML volume measured using T1W FFE sequence was significantly smaller (224.7 mm3, interquartile range [IQR] 82.50–607.95) than the other three sequences. BML volume was greatest on the CE sequence (1129.8 mm3, IQR 467.28–3166.02). Compared to CE sequence, BML volumes were slightly lower when assessed using PDFS (proportional difference = 0.79; 95% confidence interval [CI] 0.62, 1.01) and STIR sequences (proportional difference = 0.85; 95% CI 0.67, 1.08). There were strong correlations between BML volume on PDFS, STIR, and CE T1W FS sequences (ρs = 0.98). Correlations were lower between these three sequences and T1W FFE (ρs = 0.80–0.81). Intraclass correlation coefficients were excellent for proton density fat-suppressed, short-tau inversion recovery, and CE T1W FS sequences (0.991–0.995), while the ICC for T1W FFE was good at 0.88. We found no significant association between BML volumes assessed using any of the sequences and knee pain. Conclusion: T1W FFE sequences were less reliable and measured considerably smaller BML volume compared to other sequences. BML volume was larger when assessed using the contrast enhanced T1W FS though not statistically significantly different from BMLs when assessed using PDFS and STIR sequences. Advances in knowledge: This is the first study to assess BMLs by four different MRI pulse sequences on the same data set, including different fluid sensitive sequences and gradient echo type sequence

Patient and healthcare provider experience and perceptions of a preoperative rehabilitation class for lumbar discectomy: A qualitative study

Background: Lumbar disc disease is a leading cause of low back pain. Lumbar discectomy (LD) may be indicated if symptoms are not managed conservatively. Rehabilitation has traditionally been delivered postoperatively; however, there is increasing delivery preoperatively. There are few data concerning perceptions and experiences of preoperative rehabilitation. Exploring experiences of preoperative rehabilitation may help in the development and delivery of effective care for patients. Objectives: To develop an understanding of patient and healthcare provider (HCP) experiences, perspectives and preferences of preoperative LD rehabilitation, including why patients do not attend. Design: A qualitative interpretive approach using focus groups and individual interviews. Methods: Data were collected from; a) patients listed for surgery and attended the preoperative rehabilitation (October 2019 to March 2020), b) patients listed for surgery but did not attend rehabilitation, and c) HCPs involved in the delivery of rehabilitation. Data were transcribed verbatim and analysed using thematic analysis. Results/findings: Twenty participants were included, twelve patients and eight HCPs. The preoperative class was a valuable service for both patients and HCPs. It provided a solution to staffing and time pressures. It provided the required education and exercise content helping the patients along their surgery pathway. Travel distance, transportation links, parking difficulty and cost, lack of knowledge about the class aims, and previous negative experiences were barriers to patient attendance. Conclusions: For most patients and HCPs, the preoperative class was valuable. Addressing the challenges and barriers could improve attendance. Future research should focus on management of patient expectations and preferences preoperatively

Brief Report: Synovial Fluid White Blood Cell Count in Knee Osteoarthritis: Association With Structural Findings and Treatment Response

© 2016, American College of Rheumatology Objective: Osteoarthritis (OA) is a disease with a significant inflammatory component. The aim of this analysis was to determine the relationship between synovial fluid (SF) white blood cell (WBC) count and 2 parameters: disease severity and the reduction in knee pain after intraarticular (IA) steroid injection. Methods: Subjects with painful knee OA were recruited for participation in an open-label study of IA steroid therapy. Information was obtained about knee pain using the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire, and a proportion of subjects underwent magnetic resonance imaging (MRI). Prior to injection with 80 mg methylprednisolone acetate, the index knee joint was aspirated and the fluid obtained was forwarded for assessment of SF WBC count. Results: Information on SF WBC count was available for 55 subjects. An increase in WBC count category (≤100, 101–250, and 251–1,000 cells/mm3) was associated with an increase in synovial tissue volume (P = 0.028) and with other MRI-based measures of disease severity. Also, with each increase in SF WBC count category, there was a greater reduction in KOOS score after steroid injection (for WBC count of ≤100 cells/mm3 [referent], mean ± SD 12.5 ± 15.2; for WBC count of 101–250 cells/mm3, mean ± SD 21.3 ± 20.6 [β coefficient 0.279, P = 0.049]; for WBC count of 251–1,000 cells/mm3, mean ± SD 29.3 ± 15.2 [β coefficient 0.320, P = 0.024]). Conclusion: Although all participants in the analysis had SF WBC counts within the “normal” range, total SF WBC count appears to be a biomarker for synovitis on MRI and may also predict response to antiinflammatory treatment

Harmonising data collection from osteoarthritis studies to enable stratification: recommendations on core data collection from an Arthritis Research UK clinical studies group

Objective. Treatment of OA by stratifying for commonly used and novel therapies will likely improve the range of effective therapy options and their rational deployment in this undertreated, chronic disease. In order to develop appropriate datasets for conducting post hoc analyses to inform approaches to stratification for OA, our aim was to develop recommendations on the minimum data that should be recorded at baseline in all future OA interventional and observational studies. Methods. An Arthritis Research UK study group comprised of 32 experts used a Delphi-style approach supported by a literature review of systematic reviews to come to a consensus on core data collection for OA studies. Results. Thirty-five systematic reviews were used as the basis for the consensus group discussion. For studies with a primary structural endpoint, core domains for collection were defined as BMI, age, gender, racial origin, comorbidities, baseline OA pain, pain in other joints and occupation. In addition to the items generalizable to all anatomical sites, joint-specific domains included radiographic measures, surgical history and anatomical factors, including alignment. To demonstrate clinical relevance for symptom studies, the collection of mental health score, self-efficacy and depression scales were advised in addition to the above. Conclusions. Currently it is not possible to stratify patients with OA into therapeutic groups. A list of core and optional data to be collected in all OA interventional and observational studies was developed, providing a basis for future analyses to identify predictors of progression or response to treatment