Global increases in both common and rare copy number load associated with autism.

Children with autism have an elevated frequency of large, rare copy number variants (CNVs). However, the global load of deletions or duplications, per se, and their size, location and relationship to clinical manifestations of autism have not been documented. We examined CNV data from 516 individuals with autism or typical development from the population-based Childhood Autism Risks from Genetics and Environment (CHARGE) study. We interrogated 120 regions flanked by segmental duplications (genomic hotspots) for events >50 kbp and the entire genomic backbone for variants >300 kbp using a custom targeted DNA microarray. This analysis was complemented by a separate study of five highly dynamic hotspots associated with autism or developmental delay syndromes, using a finely tiled array platform (>1 kbp) in 142 children matched for gender and ethnicity. In both studies, a significant increase in the number of base pairs of duplication, but not deletion, was associated with autism. Significantly elevated levels of CNV load remained after the removal of rare and likely pathogenic events. Further, the entire CNV load detected with the finely tiled array was contributed by common variants. The impact of this variation was assessed by examining the correlation of clinical outcomes with CNV load. The level of personal and social skills, measured by Vineland Adaptive Behavior Scales, negatively correlated (Spearman's r = -0.13, P = 0.034) with the duplication CNV load for the affected children; the strongest association was found for communication (P = 0.048) and socialization (P = 0.022) scores. We propose that CNV load, predominantly increased genomic base pairs of duplication, predisposes to autism

A Systematic Review of the Literature on the Use of Rational Emotive Behaviour Therapy in Criminal Justice Work to Reduce Re-offending

A systematic review of the published literature from 1995 to 2007 considers the published evidence on the use of interventions employing Rational Emotive Behaviour Therapy in criminal justice efforts to reduce re-offending. Thirty-six studies are briefly described, summarised and appraised for research quality using a six point scale. Twenty-four studies were excluded from further analysis due to insufficiently rigorous or weak research design and method. Twelve studies were appraised as sufficiently robust to reliably inform the research interest. Further analysis of the studies indicated an association between negative emotional states and offending behaviour, some evidence of REBT effectiveness in treating emotional disturbance in offender populations, and mixed evidence of REBT effectiveness in reducing re-offending. It is concluded that interventions using REBT might be a promising approach for aiding criminal justice aims to reduce re-offending

Fracture fixation in the operative management of hip fractures (FAITH): an international, multicentre, randomised controlled trial

© 2017 Elsevier Ltd Background Reoperation rates are high after surgery for hip fractures. We investigated the effect of a sliding hip screw versus cancellous screws on the risk of reoperation and other key outcomes. Methods For this international, multicentre, allocation concealed randomised controlled trial, we enrolled patients aged 50 years or older with a low-energy hip fracture requiring fracture fixation from 81 clinical centres in eight countries. Patients were assigned by minimisation with a centralised computer system to receive a single large-diameter screw with a side-plate (sliding hip screw) or the present standard of care, multiple small-diameter cancellous screws. Surgeons and patients were not blinded but the data analyst, while doing the analyses, remained blinded to treatment groups. The primary outcome was hip reoperation within 24 months after initial surgery to promote fracture healing, relieve pain, treat infection, or improve function. Analyses followed the intention-to-treat principle. This study was registered with ClinicalTrials.gov, number NCT00761813. Findings Between March 3, 2008, and March 31, 2014, we randomly assigned 1108 patients to receive a sliding hip screw (n=557) or cancellous screws (n=551). Reoperations within 24 months did not differ by type of surgical fixation in those included in the primary analysis: 107 (20%) of 542 patients in the sliding hip screw group versus 117 (22%) of 537 patients in the cancellous screws group (hazard ratio [HR] 0·83, 95% CI 0·63–1·09; p=0·18). Avascular necrosis was more common in the sliding hip screw group than in the cancellous screws group (50 patients [9%] vs 28 patients [5%]; HR 1·91, 1·06–3·44; p=0·0319). However, no significant difference was found between the number of medically related adverse events between groups (p=0·82; appendix); these events included pulmonary embolism (two patients [\u3c1%] vs four [1%] patients; p=0·41) and sepsis (seven [1%] vs six [1%]; p=0·79). Interpretation In terms of reoperation rates the sliding hip screw shows no advantage, but some groups of patients (smokers and those with displaced or base of neck fractures) might do better with a sliding hip screw than with cancellous screws. Funding National Institutes of Health, Canadian Institutes of Health Research, Stichting NutsOhra, Netherlands Organisation for Health Research and Development, Physicians\u27 Services Incorporated

Bone regeneration: current concepts and future directions

Bone regeneration is a complex, well-orchestrated physiological process of bone formation, which can be seen during normal fracture healing, and is involved in continuous remodelling throughout adult life. However, there are complex clinical conditions in which bone regeneration is required in large quantity, such as for skeletal reconstruction of large bone defects created by trauma, infection, tumour resection and skeletal abnormalities, or cases in which the regenerative process is compromised, including avascular necrosis, atrophic non-unions and osteoporosis. Currently, there is a plethora of different strategies to augment the impaired or 'insufficient' bone-regeneration process, including the 'gold standard' autologous bone graft, free fibula vascularised graft, allograft implantation, and use of growth factors, osteoconductive scaffolds, osteoprogenitor cells and distraction osteogenesis. Improved 'local' strategies in terms of tissue engineering and gene therapy, or even 'systemic' enhancement of bone repair, are under intense investigation, in an effort to overcome the limitations of the current methods, to produce bone-graft substitutes with biomechanical properties that are as identical to normal bone as possible, to accelerate the overall regeneration process, or even to address systemic conditions, such as skeletal disorders and osteoporosis

Are large clinical trials in orthopaedic trauma justified?

Background: The objective of this analysis is to evaluate the necessity of large clinical trials using FLOW trial data. Methods: The FLOW pilot study and definitive trial were factorial trials evaluating the effect of different irrigation solutions and pressures on re-operation. To explore treatment effects over time, we analyzed data from the pilot and definitive trial in increments of 250 patients until the final sample size of 2447 patients was reached. At each increment we calculated the relative risk (RR) and associated 95% confidence interval (CI) for the treatment effect, and compared the results that would have been reported at the smaller enrolments with those seen in the final, adequately powered study. Results: The pilot study analysis of 89 patients and initial incremental enrolments in the FLOW definitive trial favored low pressure compared to high pressure (RR: 1.50, 95% CI: 0.75-3.04; RR: 1.39, 95% CI: 0.60-3.23, respectively), which is in contradiction to the final enrolment, which found no difference between high and low pressure (RR: 1.04, 95% CI: 0.81-1.33). In the soap versus saline comparison, the FLOW pilot study suggested that re-operation rate was similar in both the soap and saline groups (RR: 0.98, 95% CI: 0.50-1.92), whereas the FLOW definitive trial found that the re-operation rate was higher in the soap treatment arm (RR: 1.28, 95% CI: 1.04-1.57). Conclusions: Our findings suggest that studies with smaller sample sizes would have led to erroneous conclusions in the management of open fracture wounds. Trial registration: NCT01069315 (FLOW Pilot Study) Date of Registration: February 17, 2010, NCT00788398 (FLOW Definitive Trial) Date of Registration: November 10, 2008

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

Orthopaedic surgeons’ opinions surrounding the management of proximal humerus fractures: an international survey

© 2017, SICOT aisbl. Purpose: The purpose of this study was to survey surgeons’ preferences surrounding the management and evaluation of proximal humerus fractures internationally. Methods: A questionnaire was developed using previous literature and input from practicing orthopaedic surgeon opinion leaders. Between November 13, 2014 and December 31, 2014, the questionnaire was posted on the membership section of three major orthopaedic and shoulder surgery association websites. Survey responses were anonymous. Results: The survey was completed by 134 unique practicing orthopaedic surgeons. The majority of respondents (72%) practiced in North America while 28% practiced internationally. For displaced two-part fractures, a preference for open reduction and internal fixation (ORIF) with locking plates was identified (75%). No consensus was reached for preferred treatment of three- and four- part fractures: 37% chose ORIF with locking plates, 26% chose hemi-arthroplasty (HA), and 29% chose reverse shoulder arthroplasty (RSA). Preferred treatment types for three- and four-part fractures were marginally significantly different depending on place of practice (North America vs. international, p = 0.058). A significantly larger proportion of surgeons who had completed an upper extremity fellowship (35%) chose RSA for the treatment of three and four-part fractures, compared to those who had not (9%, p = 0.002). No consensus was observed regarding what outcome measure is best to assess function following proximal humerus fractures. Conclusions: The management of more complex, displaced proximal humerus fractures remains controversial. Additionally, there are conflicting opinions on what outcome measure is best to assess function following the treatment of proximal humerus fractures

Surgical repair <i>versus</i> conservative treatment and subacromial decompression for the treatment of rotator cuff tears

Aims The purpose of this study was to compare the effectiveness of surgical repair to conservative treatment and subacromial decompression for the treatment of chronic/degenerative tears of the rotator cuff. Materials and Methods PubMed, Cochrane database, and Medline were searched for randomized controlled trials published until March 2018. Included studies were assessed for methodological quality, and data were extracted for statistical analysis. The systematic review was conducted following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Results Six studies were included. Surgical repair resulted in a statistically significantly better Constant–Murley Score (CMS) at one year compared with conservative treatment (mean difference 6.15; p = 0.002) and subacromial decompression alone (mean difference 5.81; p = 0.0004). In the conservatively treated group, 11.9% of patients eventually crossed over to surgical repair. Conclusion The results of this review show that surgical repair results in significantly improved outcomes when compared with either conservative treatment or subacromial decompression alone for degenerative rotator cuff tears in older patients. However, the magnitude of the difference in outcomes between surgery and conservative treatment may be small and the ‘success rate’ of conservative treatment may be high, allowing surgeons to be judicious in choosing those patients who are most likely to benefit from surgery. Cite this article: Bone Joint J 2019;101-B:1100–1106. </jats:sec