12-year survival analysis of 322 Hintegra total ankle arthroplasties from an independent center

Background and purpose — Total ankle arthroplasties (TAAs) have larger revision rates than hip and knee implants. We examined the survival rates of our primary TAAs, and what different factors, including the cause of arthritis, affect the success and/or revision rate.Patients and methods — From 2004 to 2016, 322 primary Hintegra TAAs were implanted: the 2nd generation implant from 2004 until mid-2007 and the 3rd generation from late 2007 to 2016. A Cox proportional hazards model evaluated sex, age, primary diagnosis, and implant generation, pre- and postoperative angles and implant position as risk factors for revision.Results — 60 implants (19%) were revised, the majority (n = 34) due to loosening. The 5-year survival rate (95% CI) was 75% (69–82) and the 10-year survival rate was 68% (60–77). There was a reduced risk of revision, per degree of increased postoperative medial distal tibial angle at 0.84 (0.72–0.98) and preoperative talus angle at 0.95 (0.90–1.00), indicating that varus ankles may have a larger revision rate. Generation of implant, sex, primary diagnosis, and most pre- and postoperative radiological angles did not statistically affect revision risk.Interpretation — Our revision rates are slightly above registry rates and well above those of the developer. Most were revised due to loosening; no difference was demonstrated with the 2 generations of implant used. Learning curve and a low threshold for revision could explain the high revision rate.

Arthritis in the ankle often develops earlier than in the hip or knee, and 70% have a traumatic etiology (Saltzman et al. 2005, Brown et al. 2006). Total ankle arthroplasty (TAA) can be indicated for severe arthritis in the ankle joint, but the anatomical preconditions, like a small surface area and high stress from compression and torque (Bouguecha et al. 2011, Kakkar and Siddique 2011), makes it less durable than hip and knee prosthetics. The Hintegra TAA, a 3-component mobile bearing, uncemented implant (Hintermann et al. 2004) is widely used and results from the development center demonstrate survival rates of 94% and 84% after 5 and 10 years’ follow-up (Barg et al. 2013). This is considerably more than the survival rates from national registries. Labek et al. (2011) demonstrated that development centers report only half of the revision rate that can be found in the few existing national registers. In a systematic review of primary Agility total ankle arthroplasty (DePuy Synthes Orthopedics, Warsaw, IN, USA), the author (Roukis 2012) found that the incidence of complications increased from 7% to 12%, in studies where the inventor was excluded. Similar results were found by Prissel and Roukis (2013), who found an increased incidence of complications from 6% to 13% in studies where the inventor or faculty consultants were excluded. These studies indicated the risk of selection (inventor) and publication (conflict of interest) bias.Planning and surgical technique, including significant experience, are mandatory for a successful outcome. The better result from development centers may reflect, besides the above-mentioned bias, that there is a long learning curve and that the indication for revision surgery varies.We examined the survival rates of primary Hintegra TAAs performed at Hvidovre Hospital, with revision rate as outcome. We report primary diagnosis for primary TAA and examine whether sex, generation of the implant, preoperative angles and implant position affect the revision rate.     

Evaluation of vilazodone for the treatment of depressive and anxiety disorders

Introduction: Major Depressive Disorder (MDD) and General Anxiety Disorder (GAD) significantly contribute to the global burden of disease. Vilazodone, a combined serotonin reuptake inhibitor and 5-HT1A partial agonist, is an approved therapy for the treatment of MDD and which has been further investigated for GAD.

Areas covered: This article covers the pharmacokinetics and pharmacodynamics of vilazodone and provides an evaluation of the clinical usefulness of vilazodone for the treatment of MDD and anxiety disorders. A literature search was performed using PubMed/MEDLINE, Web of Science and the Cochrane Library.

Expert opinion: Studies have shown that vilazodone is significantly superior to placebo. However, vilazodone cannot as yet be recommended as a first-line treatment option for MDD as it is unclear whether the drug’s dual mechanism of action provides greater efficacy than prevailing treatment options. Moreover, more phase IV studies are needed to establish its efficacy and long-term safety in larger and more diverse populations. Although vilazodone may have an additional advantage for the treatment of anxiety symptoms in MDD, here also additional studies are required to confirm its efficacy over and above SSRI alternatives and other antidepressant treatments. Therefore, presently, vilazodone should be considered as a second- or third-line treatment option for MDD and GAD.     

Prevalence and Correlates of Mental Health Problems in Norwegian Peacekeepers 18–38 Years Postdeployment

Peacekeeping missions involve experiences that may impact the mental health of participating soldiers. However, research on the long-term mental health consequences of peacekeeping is sparse. The present study aimed to find the prevalence of mental health problems (MHPs), possible MHP predictors, and associations between predictors and MHPs in Norwegian peacekeepers 18–38 years after deployment to a United Nations peacekeeping mission. We used data from a cross-sectional, postdeployment survey of Norwegian peacekeepers who served in Lebanon between 1978 and 1998 (N = 10,605). Participants were assessed for posttraumatic stress disorder (PTSD); anxiety; depression; insomnia; alcohol misuse; drug misuse; and exposure to pre-, peri-, and postdeployment stressors. Logistic regressions were executed to explore key variables associated with MHPs. Total MHP prevalence was 15.1%, 95% CI [14.4, 15.8]. The estimates for specific disorders were 0.1% for drug misuse, 3.4% for alcohol misuse, 4.0% for depression, 6.2% for PTSD, 6.4% for anxiety, and 9.3% for insomnia. Postdeployment stressors, OR = 1.91, 95% CI [1.79, 2.04]; employment status, OR = 1.41, 95% CI [1.33, 1.48]; and traumatic exposure during deployment, OR = 1.11, 95% CI [1.09, 1.12], were positively related to PTSD, χ2(17, N = 8,568) = 1,791.299, p < .001. Similar patterns were found for the other MHPs. Considering that most participants (84.9%) reported low symptom levels, our findings challenge the widespread public perception that most peacekeepers have MHPs. Moreover, our results indicate that future peacekeepers should be prepared for challenges they may face not only during deployment but also in the years following their homecoming.     

Loss of function,missense, and intronic variants in NOTCH1 confer different risks for left ventricular outflow tract obstructive heart defects in two European cohorts

Loss of function variants in NOTCH1 cause left ventricular outflow tract obstructive defects (LVOTO). However, the risk conferred by rare and noncoding variants in NOTCH1 for LVOTO remains largely uncharacterized. In a cohort of 49 families affected by hypoplastic left heart syndrome, a severe form of LVOTO, we discovered predicted loss of function NOTCH1 variants in 6% of individuals. Rare or low-frequency missense variants were found in 16% of families. To make a quantitative estimate of the genetic risk posed by variants in NOTCH1 for LVOTO, we studied associations of 400 coding and noncoding variants in NOTCH1 in 1,085 cases and 332,788 controls from the UK Biobank. Two rare intronic variants in strong linkage disequilibrium displayed significant association with risk for LVOTO amongst European-ancestry individuals. This result was replicated in an independent analysis of 210 cases and 68,762 controls of non-European and mixed ancestry. In conclusion, carrying rare predicted loss of function variants in NOTCH1 confer significant risk for LVOTO. In addition, the two intronic variants seem to be associated with an increased risk for these defects. Our approach demonstrates the utility of population-based data sets in quantifying the specific risk of individual variants for disease-related phenotypes.     

Adiposity and physical activity as predictors of cardiovascular mortality.

OBJECTIVE: To investigate whether cardiovascular mortality related to obesity could be modified by physical activity. DESIGN: Mortality follow-up. SETTING: Population study. PARTICIPANTS: Participants in a health survey: 34 868 women and 32 872 men free from known cardiovascular disease or diabetes at baseline. MAIN OUTCOME MEASURES: Total cardiovascular mortality. MAIN RESULTS: During 16 years of follow-up, 3026 women and 3526 men had died from cardiovascular causes. In middle age, obesity [body mass index (BMI) of 30 or higher] was associated with increased risk of cardiovascular death, but the association weakened with age. After 70, there was no association between BMI and cardiovascular death. At all ages, a lower level of physical activity was associated with a higher cardiovascular mortality. In women with high physical activity, indicated by at least 30 min of moderate to vigorous activity more than once a week, cardiovascular mortality was only slightly higher in the obese compared to lean women (adjusted relative risk, 1.27; 95% confidence interval, 0.80-2.00). In men with high physical activity, cardiovascular mortality was, however, significantly higher among the obese (relative risk, 1.62; 95% confidence interval, 1.09-2.40). In both genders cardiovascular mortality was substantially higher in obese people who reported no regular physical activity compared to obese people with a high level of physical activity. CONCLUSION: In obese women, being highly active may, to a large extent, compensate for the risk-increasing effect of being obese, whereas in obese men who engage in a high level of physical activity, the risk of cardiovascular death may be higher than in lean and equally active men.