Searching for consensus in the approach to patients with chronic lateral ankle instability: ask the expert.

PURPOSE: The purpose of this study is to propose recommendations for the treatment of patients with chronic lateral ankle instability (CAI) based on expert opinions. METHODS: A questionnaire was sent to 32 orthopaedic surgeons with clinical and scientific experience in the treatment of CAI. The questions were related to preoperative imaging, indications and timing of surgery, technical choices, and the influence of patient-related aspects. RESULTS: Thirty of the 32 invited surgeons (94%) responded. Consensus was found on several aspects of treatment. Preoperative MRI was routinely recommended. Surgery was considered in patients with functional ankle instability after 3-6 months of non-surgical treatment. Ligament repair is still the treatment of choice in patients with mechanical instability; however, in patients with generalized laxity or poor ligament quality, lateral ligament reconstruction (with grafting) of both the ATFL and CFL should be considered. CONCLUSIONS: Most surgeons request an MRI during the preoperative planning. There is a trend towards earlier surgical treatment (after failure of non-surgical treatment) in patients with mechanical ligament laxity (compared with functional instability) and in high-level athletes. This study proposes an assessment and a treatment algorithm that may be used as a recommendation in the treatment of patients with CAI. LEVEL OF EVIDENCE: V.

Absence of evidence for increase in risk for autism or attention-deficit hyperactivity disorder following antidepressant exposure during pregnancy: a replication study.

Multiple studies have examined the risk of prenatal antidepressant exposure and risk for autism spectrum disorder (ASD) or attention-deficit hyperactivity disorder (ADHD), with inconsistent results. Precisely estimating such risk, if any, is of great importance in light of the need to balance such risk with the benefit of depression and anxiety treatment. We developed a method to integrate data from multiple New England health systems, matching offspring and maternal health data in electronic health records to characterize diagnoses and medication exposure. Children with ASD or ADHD were matched 1:3 with children without neurodevelopmental disorders. Association between maternal antidepressant exposure and ASD or ADHD liability was examined using logistic regression, adjusting for potential sociodemographic and psychiatric confounding variables. In new cohorts of 1245 ASD cases and 1701 ADHD cases, along with age-, sex- and socioeconomic status matched controls, neither disorder was significantly associated with prenatal antidepressant exposure in crude or adjusted models (adjusted odds ratio 0.90, 95% confidence interval 0.50-1.54 for ASD; 0.97, 95% confidence interval 0.53-1.69 for ADHD). Pre-pregnancy antidepressant exposure significantly increased risk for both disorders. These results suggest that prior reports of association between prenatal antidepressant exposure and neurodevelopmental disease are likely to represent a false-positive finding, which may arise in part through confounding by indication. They further demonstrate the potential to integrate data across electronic health records studies spanning multiple health systems to enable efficient pharmacovigilance investigation.

Consensus in chronic ankle instability: aetiology, assessment, surgical indications and place for arthroscopy.

Ankle sprains are the most common injuries sustained during sports activities. Most ankle sprains recover fully with non-operative treatment but 20-30% develop chronic ankle instability. Predicting which patients who sustain an ankle sprain will develop instability is difficult. This paper summarises a consensus on identifying which patients may require surgery, the optimal surgical intervention along with treatment of concomitant pathology given the evidence available today. It also discusses the role of arthroscopic treatment and the anatomical basis for individual procedures.

Peripheral blood gene expression signature differentiates children with autism from unaffected siblings.

Autism spectrum disorder (ASD) is one of the most prevalent neurodevelopmental disorders with high heritability, yet a majority of genetic contribution to pathophysiology is not known. Siblings of individuals with ASD are at increased risk for ASD and autistic traits, but the genetic contribution for simplex families is estimated to be less when compared to multiplex families. To explore the genomic (dis-) similarity between proband and unaffected sibling in simplex families, we used genome-wide gene expression profiles of blood from 20 proband-unaffected sibling pairs and 18 unrelated control individuals. The global gene expression profiles of unaffected siblings were more similar to those from probands as they shared genetic and environmental background. A total of 189 genes were significantly differentially expressed between proband-sib pairs (nominal p < 0.01) after controlling for age, sex, and family effects. Probands and siblings were distinguished into two groups by cluster analysis with these genes. Overall, unaffected siblings were equally distant from the centroid of probands and from that of unrelated controls with the differentially expressed genes. Interestingly, five of 20 siblings had gene expression profiles that were more similar to unrelated controls than to their matched probands. In summary, we found a set of genes that distinguished probands from the unaffected siblings, and a subgroup of unaffected siblings who were more similar to probands. The pathways that characterized probands compared to siblings using peripheral blood gene expression profiles were the up-regulation of ribosomal, spliceosomal, and mitochondrial pathways, and the down-regulation of neuroreceptor-ligand, immune response and calcium signaling pathways. Further integrative study with structural genetic variations such as de novo mutations, rare variants, and copy number variations would clarify whether these transcriptomic changes are structural or environmental in origin.

Patterns of temperament and character in subjects with obsessive-compulsive disorder.

BACKGROUND: The purpose of this study was to assess the temperament and character patterns of obsessive-compulsive disorder (OCD) patients and to investigate the relationship between patterns of temperament and character and the severity of obsessive-compulsive symptoms. METHOD: The subjects were 40 patients who met DSM-IV criteria for OCD and 40 age-, sex-, and IQ-matched healthy controls. All subjects completed Cloninger's Temperament and Character Inventory. Other instruments included the Yale-Brown Obsessive Compulsive Scale, the Beck Depression Inventory, and the Beck Anxiety Inventory. RESULTS: OCD patients showed significantly higher scores of harm avoidance and lower scores of novelty seeking and self-directedness compared with healthy comparison subjects. In addition, the high harm avoidance and low self-directedness scores are correlated with a greater severity of obsessive-compulsive symptoms in OCD subjects (multiple regression analysis, beta = 0.39, t = 2.54, df = 34, p = .016; beta = -0.41, t = 2.46, df = 34, p = .019, respectively). CONCLUSION: OCD patients had distinct patterns of temperament and character compared with healthy comparison subjects. In addition, these patterns are specifically related to the severity of obsessive-compulsive symptoms.