Botulinum Toxin Injection for Internal Rotation Contractures in Brachial Plexus Birth Palsy. A Minimum 5-Year Prospective Observational Study.

BACKGROUND: Brachial plexus birth palsy is frequently associated with internal rotation contractures of the shoulder as a result of muscle imbalance. The purpose of this study is to assess the effect of botulinum toxin A (BTX-A) injection in the subscapular (SC) muscle on external rotation and the need for tendon transfer for external rotation of the shoulder. METHODS: A prospective comparative study was performed including 15 consecutive patients treated with BTX-A and a historic control group of 67 patients with mean age 30 months (SD 10). The BTX-A injection (2 IU/kg body weight) was performed immediately following MRI under general anesthesia in the SC muscle. Passive external rotation, the need for tendon transfer surgery, glenohumeral deformity, and muscle degeneration were evaluated. The hazard ratio for no relapse of internal rotation contracture after BTX-A injection compared with no BTX-A injection was calculated. RESULTS: In the BTX-A group, the passive external rotation in adduction increased from -1 degree (95% CI, -10 to 8) to 32 degrees (95% CI, 17-46) at 3 months and 6 patients were indicated for surgery compared with a decline from -2 degrees (95% CI, -7 to 3) to -11 degrees (95% CI, -17 to -6) in the control group with 66 indications for surgery. At 5 years of follow-up, 10 patients in the BTX-A group were indicated for surgery with a hazard ratio of 4.0 (95% CI, 1.9 to 8.4). CONCLUSIONS: BTX-A injection in the SC muscle of brachial plexus birth palsy patients can reduce internal rotation contractures and subsequently the need for tendon transfer surgery. At 5 years of follow-up a relapse was seen in 67% of the patients treated with BTX-A. Because at MRI less SC degeneration was found in the good responders on BTX-A treatment, this group seems to be the best target group. Further research is needed on patient selection for BTX-A injection including glenohumeral deformity, SC degeneration, as well as doses of BTX-A to be used. LEVEL OF EVIDENCE: Level II-prospective comparative study.

Cannabinoids for Medical Use: A Systematic Review and Meta-analysis.

IMPORTANCE: Cannabis and cannabinoid drugs are widely used to treat disease or alleviate symptoms, but their efficacy for specific indications is not clear. OBJECTIVE: To conduct a systematic review of the benefits and adverse events (AEs) of cannabinoids. DATA SOURCES: Twenty-eight databases from inception to April 2015. STUDY SELECTION: Randomized clinical trials of cannabinoids for the following indications: nausea and vomiting due to chemotherapy, appetite stimulation in HIV/AIDS, chronic pain, spasticity due to multiple sclerosis or paraplegia, depression, anxiety disorder, sleep disorder, psychosis, glaucoma, or Tourette syndrome. DATA EXTRACTION AND SYNTHESIS: Study quality was assessed using the Cochrane risk of bias tool. All review stages were conducted independently by 2 reviewers. Where possible, data were pooled using random-effects meta-analysis. MAIN OUTCOMES AND MEASURES: Patient-relevant/disease-specific outcomes, activities of daily living, quality of life, global impression of change, and AEs. RESULTS: A total of 79 trials (6462 participants) were included; 4 were judged at low risk of bias. Most trials showed improvement in symptoms associated with cannabinoids but these associations did not reach statistical significance in all trials. Compared with placebo, cannabinoids were associated with a greater average number of patients showing a complete nausea and vomiting response (47% vs 20%; odds ratio [OR], 3.82 [95% CI, 1.55-9.42]; 3 trials), reduction in pain (37% vs 31%; OR, 1.41 [95% CI, 0.99-2.00]; 8 trials), a greater average reduction in numerical rating scale pain assessment (on a 0-10-point scale; weighted mean difference [WMD], -0.46 [95% CI, -0.80 to -0.11]; 6 trials), and average reduction in the Ashworth spasticity scale (WMD, -0.36 [95% CI, -0.69 to -0.05]; 7 trials). There was an increased risk of short-term AEs with cannabinoids, including serious AEs. Common AEs included dizziness, dry mouth, nausea, fatigue, somnolence, euphoria, vomiting, disorientation, drowsiness, confusion, loss of balance, and hallucination. CONCLUSIONS AND RELEVANCE: There was moderate-quality evidence to support the use of cannabinoids for the treatment of chronic pain and spasticity. There was low-quality evidence suggesting that cannabinoids were associated with improvements in nausea and vomiting due to chemotherapy, weight gain in HIV infection, sleep disorders, and Tourette syndrome. Cannabinoids were associated with an increased risk of short-term AEs.

Cemented total hip arthroplasty revisions in patients of eighty years and older.

PURPOSE: It is often a difficult decision whether it is safe to perform revision hip surgery in a patient of 80 years and older. Therefore we evaluated the results of cemented revisions in these elderly patients. METHODS: Clinical data, radiographs and complications of 49 consecutive cup and/or stem revisions in 48 patients were prospectively collected. The average age of the patients at surgery was 84 years (range, 80-92). We performed Kaplan-Meier (KM) analysis and also a competing risk (CR) analysis because in this series the presence of a competing event (i.e. death) prevents the occurrence of endpoint rerevision. RESULTS: Twenty-nine patients (30 hips) died without rerevision during follow-up and their data was included. The average follow-up of the 16 surviving patients was eight years (range, six to 13). Six re-operations were performed, of which three were re-revisions. Eight-year survivorship was 91.6% (95% confidence interval (CI) 76-97%) for endpoint re-revision for any reason. With the CR analysis we calculated that due to the increasing number of competing events, the KM analysis overestimates the failure rate with 32% for this endpoint. The average Harris hip score improved from 49 to 74. Mortality within three months after surgery was 6%. One postoperative fracture occurred and six hips dislocated. CONCLUSION: Cemented revisions can provide satisfying results in patient of 80 years and older with acceptable survivorship and complication rates.

Which implant should we use for primary total hip replacement? A systematic review and meta-analysis.

BACKGROUND: Many total hip implants are currently available on the market worldwide. We aimed to estimate the probability of revision surgery at ten years for each individual total hip implant and to compare these estimates with the National Institute for Health and Care Excellence (NICE) benchmark. METHODS: We performed a meta-analysis of cohort studies. The methodological quality was assessed with use of the Assessment of Quality in Lower Limb Arthroplasty (AQUILA) checklist. We searched PubMed, Embase, Web of Science, and the Cochrane Library. Additionally, national joint registries that were full members of the International Society of Arthroplasty Registers (ISAR) were hand searched. Studies in which the authors reported the survival probability for either the acetabular or the femoral component of primary total hip replacements with use of revision for any reason or for aseptic loosening at ten years as the end point, with at least 100 implants at baseline, and in which at least 60% of the patients had primary osteoarthritis were eligible for inclusion. RESULTS: The search strategy revealed 5513 papers describing survival probabilities for thirty-four types of acetabular components and thirty-two types of femoral components. Eight types of acetabular cups and fifteen types of femoral stems performed better than the NICE benchmark. CONCLUSIONS: We recommend that surgeons performing a primary total hip replacement use an implant that outperforms the NICE benchmarks.

Genes involved in the osteoarthritis process identified through genome wide expression analysis in articular cartilage; the RAAK study.

OBJECTIVE: Identify gene expression profiles associated with OA processes in articular cartilage and determine pathways changing during the disease process. METHODS: Genome wide gene expression was determined in paired samples of OA affected and preserved cartilage of the same joint using microarray analysis for 33 patients of the RAAK study. Results were replicated in independent samples by RT-qPCR and immunohistochemistry. Profiles were analyzed with the online analysis tools DAVID and STRING to identify enrichment for specific pathways and protein-protein interactions. RESULTS: Among the 1717 genes that were significantly differently expressed between OA affected and preserved cartilage we found significant enrichment for genes involved in skeletal development (e.g. TNFRSF11B and FRZB). Also several inflammatory genes such as CD55, PTGES and TNFAIP6, previously identified in within-joint analyses as well as in analyses comparing preserved cartilage from OA affected joints versus healthy cartilage were among the top genes. Of note was the high up-regulation of NGF in OA cartilage. RT-qPCR confirmed differential expression for 18 out of 19 genes with expression changes of 2-fold or higher, and immunohistochemistry of selected genes showed a concordant change in protein expression. Most of these changes associated with OA severity (Mankin score) but were independent of joint-site or sex. CONCLUSION: We provide further insights into the ongoing OA pathophysiological processes in cartilage, in particular into differences in macroscopically intact cartilage compared to OA affected cartilage, which seem relatively consistent and independent of sex or joint. We advocate that development of treatment could benefit by focusing on these similarities in gene expression changes and/or pathways.

A meta-analysis of genome-wide association studies identifies novel variants associated with osteoarthritis of the hip.

OBJECTIVES: Osteoarthritis (OA) is the most common form of arthritis with a clear genetic component. To identify novel loci associated with hip OA we performed a meta-analysis of genome-wide association studies (GWAS) on European subjects. METHODS: We performed a two-stage meta-analysis on more than 78,000 participants. In stage 1, we synthesised data from eight GWAS whereas data from 10 centres were used for 'in silico' or 'de novo' replication. Besides the main analysis, a stratified by sex analysis was performed to detect possible sex-specific signals. Meta-analysis was performed using inverse-variance fixed effects models. A random effects approach was also used. RESULTS: We accumulated 11,277 cases of radiographic and symptomatic hip OA. We prioritised eight single nucleotide polymorphism (SNPs) for follow-up in the discovery stage (4349 OA cases); five from the combined analysis, two male specific and one female specific. One locus, at 20q13, represented by rs6094710 (minor allele frequency (MAF) 4%) near the NCOA3 (nuclear receptor coactivator 3) gene, reached genome-wide significance level with p=7.9×10(-9) and OR=1.28 (95% CI 1.18 to 1.39) in the combined analysis of discovery (p=5.6×10(-8)) and follow-up studies (p=7.3×10(-4)). We showed that this gene is expressed in articular cartilage and its expression was significantly reduced in OA-affected cartilage. Moreover, two loci remained suggestive associated; rs5009270 at 7q31 (MAF 30%, p=9.9×10(-7), OR=1.10) and rs3757837 at 7p13 (MAF 6%, p=2.2×10(-6), OR=1.27 in male specific analysis). CONCLUSIONS: Novel genetic loci for hip OA were found in this meta-analysis of GWAS.

Willingness to undergo surgery again validated clinically important differences in health-related quality of life after total hip replacement or total knee replacement surgery.

OBJECTIVES: To determine clinically important differences (CIDs) in health-related quality of life (HRQoL) after total hip replacement (THR) or total knee replacement (TKR) surgery, using the Short Form 36 (SF-36). STUDY DESIGN AND SETTING: SF-36 scores were collected 2 weeks before and at 1.5-6 years after joint replacement in 586 THR and 400 TKR patients in a multicenter cohort study. We calculated distribution-based CIDs (0.8 standard deviations of the preoperative score) for each SF-36 subscale. Responders (patients with an improvement in HRQoL ≥ CID of a particular subscale) were compared with nonresponders using an external validation question: willingness to undergo surgery again. RESULTS: CIDs for THR/TKR were physical functioning (PF), 17.9/16.7; role-physical (RP), 31.1/33.4; bodily pain (BP), 16.8/16.2; general health, 15.5/15.7; vitality, 17.3/16.7; social functioning (SF), 22.0/19.9; role-emotional, 33.7/33.6; and mental health, 14.8/14.1. CIDs of PF, RP, BP, and SF were validated by the validation question. CONCLUSION: Valid and precise CIDs are estimated of PF, RP, BP, and SF, which are relevant in HRQoL subscales for THR and TKR patients. CIDs of all other subscales should be used cautiously.

How to deal with lost to follow-up in total knee arthroplasty : a new method based on the competing risks approach.

PURPOSE: The aim of this study was to develop a more accurate method to deal with patients lost to follow-up based on the competing risks approach. METHODS: A cohort of 112 patients who received 143 primary cemented total knee arthroplasties forms the basis for this study. Follow-up was up to 25 years. The new method for dealing with lost to follow-up accounts for competing events (i.e. death and failure of a prosthesis) using the cumulative incidence estimator and estimates time to event for patients lost to follow-up using national demographic registries. The results of this new method were compared with the worst case scenario estimated by Kaplan-Meier. RESULTS: Six different situations were identified covering all possible situations in long-term follow-up for total knee arthroplasty. The new method--considering all patients lost to follow-up as revised--showed a twofold reduction in revision rate compared to the traditional worst case scenario using Kaplan-Meier. CONCLUSIONS: Lost to follow-up should be prevented whenever possible, but this may be unavoidable for long-term follow-up studies. In situations where lost to follow-up does occur, the new proposed method offers an efficient and valid approach to deal with this problem.

Patients with severe radiographic osteoarthritis have a better prognosis in physical functioning after hip and knee replacement: a cohort-study.

INTRODUCTION: Although Total Hip and Knee Replacements (THR/TKR) improve Health-Related Quality of Life (HRQoL) at the group level, up to 30% of patients are dissatisfied after surgery due to unfulfilled expectations. We aimed to assess whether the pre-operative radiographic severity of osteoarthritis (OA) is related to the improvement in HRQoL after THR or TKR, both at the population and individual level. METHODS: In this multi-center observational cohort study, HRQoL of OA patients requiring THR or TKR was measured 2 weeks before surgery and at 2-5 years follow-up, using the Short-Form 36 (SF36). Additionally, we measured patient satisfaction on a 11-point Numeric Rating Scale (NRSS). The radiographic severity of OA was classified according to Kellgren and Lawrence (KL) by an independent experienced musculoskeletal radiologist, blinded for the outcome. We compared the mean improvement and probability of a relevant improvement (defined as a patients change score ≥ Minimal Clinically Important Difference) between patients with mild OA (KL Grade 0-2) and severe OA (KL Grade 3+4), whilst adjusting for confounders. RESULTS: Severe OA patients improved more and had a higher probability of a relevant improvement in physical functioning after both THR and TKR. For TKR patients with severe OA, larger improvements were found in General Health, Vitality and the Physical Component Summary Scale. The mean NRSS was also higher in severe OA TKR patients. DISCUSSION: Patients with severe OA have a better prognosis after THR and TKR than patients with mild OA. These findings might help to prevent dissatisfaction after THR and TKR by means of patient selection or expectation management.

Socio-economic position has no effect on improvement in health-related quality of life and patient satisfaction in total hip and knee replacement: a cohort study.

INTRODUCTION: Considerable evidence suggests that patients with more advantaged Socio-Economic Positions undergo Total Hip and Knee Replacement (THR/TKR) more often, despite having a lower need. We questioned whether more disadvantaged Socio-Economic Position is associated with an lower improvement in Health-Related Quality of Life (HRQoL) and a lower patient satisfaction after THR/TKR. METHODS: Patients who underwent primary THR/TKR in one academic and three community hospitals between 2005 and 2009, were eligible for inclusion. The highest completed levels of schooling were aggregated to index social class. We compared the improvement in HRQoL and postoperative satisfaction with surgery (measured using the Short-Form 36 (SF36) and an 11-point numeric rating scale of satisfaction) between the aggregated groups of highest completed levels of schooling, using linear mixed model analysis, with center as a random effect and potential confounders (i.e. age, gender, Body Mass Index and Charnley's comorbidity classification) as fixed effects. RESULTS: 586 THR patients and 400 TKR patients (40% of all eligible patients) agreed to participate and completed all questionnaires sufficiently. We found no differences in HRQoL improvement in any dimension of the SF36 in THR patients. Patients with a higher completed level of schooling had a larger improvement in role-physical (9.38 points, 95%-CI:0.34-18.4), a larger improvement in general health (3.67 points, 95%-CI:0.56-6.79) and a smaller improvement in mental health (3.60 points, 95%-CI:0.82-6.38) after TKR. Postoperative patient satisfaction did not differ between different highest completed level of schooling groups. DISCUSSION: Completed level of schooling has no effect on the improvement in HRQoL and patient satisfaction in a Dutch THR population and a small effect in a similar TKR population. Undertreatment of patients with more disadvantaged Socio-Economic Position cannot be justified, given the similar improvement in HRQoL and postoperative level of satisfaction with surgery between the social groups examined.