Patent foramen ovale closure in patients with transient ischemia attack/stroke

Paradoxical embolism through a patent foramen ovale (PFO) has been recognized as a potential cause of transient ischemia attack (TIA) and stroke especially in younger patients. The therapeutic options are medical treatment (antiaggregation or anticoagulation) with an annual recurrence rate of 3% to 4% for stroke or TIA, surgical PFO closure, or catheter closure. Randomized studies are ongoing; however, the results will not be available soon. Since August 1994, we have attempted catheter closure of a PFO in 281 patients (age 17 to 79 years, mean 46.8 +/- 13.2) with paradoxical embolism. Of these, 184 patients had at least one embolic stroke, 112 patients at least one TIA, and 15 patients at least one peripheral embolism. The diameter of the PFO, measured with a balloon catheter, ranged from 3 mm to 24 mm with a mean of 10 +/- 3.5 mm. Implantation of the occluder was technically successful in all patients (two attempts in four patients). Seven different devices were used: 26 Sideris buttoned, 11 ASDOS, 19 Angel Wings, 98 PFO-Star, 37 Cardioseal-Starflex, 57 Amplatzer and, 33 Helex devices. One patient suffered from septicemia and subsequently died. In 2 patients, device embolization occurred during or after the procedure (1 Sideris, 1 PFO-Star; catheter retrieval successful). Thirty-seven patients had other minor complications without long-term sequelae: atrial fibrillation within the first weeks after implantation in five patients, asymptomatic thrombus on the device at routine transesophageal echocardiogram (TEE) in 7 patients (1 Angel Wings, 1 ASDOS, 1 CardioSeal, 4 PFO-Star), and device frame fracture in 25 patients (2 Sideris, 4 ASDOS, 1 Angel Wings, 1 CardioSeal, 17 PFO-Star). No complications occurred with the newer devices (Amplatzer and Helex). A residual shunt after 6 months was found in 5.5% of the patients who had completed their 6-month TEE follow-up. In two patients, a second occluder was implanted because of a residual shunt. During a follow-up period of 1 month to 71 months (mean 12 +/- 16 months, 268 patient years), a recurrence of an embolic event (seven TIA, two stroke) occurred in eight patients. None of these occurred with the newer devices (Amplatzer, Helex). Freedom from recurrence of the combined end point of TIA, ischemic stroke, and peripheral embolism was 95.7% (95% CI: 89.0%-98.4%) at 1 year and 94.1% (95% CI: 80.1-98.4%) at 3 years. Catheter PFO closure is a technically simple procedure. With the newer devices and increasing experience, the success rate has improved and the complication rate has decreased. The advantage of the procedure is that closing the defect means a causal treatment. However, catheter closure of PFO despite a very low morbidity has inherent potential risks like any other interventional procedure. Furthermore, selection of patients who definitely have PFO as the cause of their cerebral event has not been defined. For these reasons, further studies are warranted.     

The psychology of ‘regrettable substitutions’: examining consumer judgements of Bisphenol A and its alternatives

Bisphenol A is a chemical used to make certain types of plastics and is found in numerous consumer products. Because scientific studies have raised concerns about Bisphenol A’s potential impact on human health, it has been removed from some (but not all) products. What many consumers do not know, however, is that Bisphenol A is often replaced with other, less-studied chemicals whose health implications are virtually unknown. This type of situation is known as a potential ‘regrettable substitution’, because the substitute material might actually be worse than the material that it replaces. Regrettable substitutions are a common concern among policymakers, and they are a real-world manifestation of the tension that can exist between the desire to avoid risk (known possible consequences that might or might not occur) and ambiguity (second-order uncertainty), which is itself aversive. In this article, we examine how people make such trade-offs using the example of Bisphenol A. Using data from Study 1, we show that people have inconsistent preferences towards these alternatives and that choice is largely determined by irrelevant contextual factors such as the order in which the alternatives are evaluated. Using data from Study 2, we further demonstrate that when people are informed of the presence of substitute chemicals, labelling the alternative product as ‘free’ of Bisphenol A causes them to be significantly more likely to choose the alternative despite its ambiguity. We discuss the relevance of these findings for extant psychological theories as well as their implications for risk, policy and health communication.     

Prognosis of Mild Cognitive Impairment in General Practice: Results of the German AgeCoDe Study

PURPOSE

The concept of mild cognitive impairment (MCI) has recently been introduced into the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) as mild neurocognitive disorder, making it a formal diagnosis. We investigated the prognostic value of such a diagnosis and analyzed the determinants of the future course of MCI in the AgeCoDe study (German Study on Ageing, Cognition, and Dementia in Primary Care Patients).

METHODS

We recruited 357 patients with MCI aged 75 years or older from primary care practices and conducted follow-up with interviews for 3 years. Depending on the course of impairment over time, the patients were retrospectively split into 4 groups representing remittent, fluctuating, stable, and progressive courses of MCI. We performed ordinal logistic regression analysis and classification and regression tree (CART) analysis.

RESULTS

Overall, 41.5% of the patients had remission of symptoms with normal cognitive function 1.5 and 3 years later, 21.3% showed a fluctuating course, 14.8% had stable symptoms, and 22.4% had progression to dementia. Patients were at higher risk for advancing from one course to the next along this spectrum if they had symptoms of depression, impairment in more than 1 cognitive domain, or more severe cognitive impairment, or were older. The result on a test of the ability to learn and reproduce new material 10 minutes later was the best indicator at baseline for differentiating between remittent and progressive MCI. Symptoms of depression modified the prognosis.

CONCLUSIONS

In primary care, about one-quarter of patients with MCI have progression to dementia within the next 3 years. Assessments of memory function and depressive symptoms are helpful in predicting a progressive vs a remittent course. When transferring the concept of MCI into clinical diagnostic algorithms (eg, DSM-5), however, we should not forget that three-quarters of patients with MCI stayed cognitively stable or even improved within 3 years. They should not be alarmed unnecessarily by receiving such a diagnosis.     

Heat Stress is Associated with Reduced Health Status in Pulmonary Arterial Hypertension: A Prospective Study Cohort

Background

Summer heat waves with temperature extremes are becoming more frequent with growing numbers in morbidity and mortality in patients with respiratory diseases. The aim of this study was to evaluate the ramifications of heat stress (temperature >25 °C) on the health status of patients with pulmonary arterial hypertension (PAH).

Methods

Fifteen patients with PAH (mean age = 66.7 ± 5.2 years) continuously wore an accelerometer from April 1 to September 30, 2011, and their daily step count was recorded. In addition, patients kept a diary to record data on seven standardized questions regarding their daily symptoms. Echocardiography, 6-minute walk test, NTproBNP, and Modified Medical Research Council Scale (MMRC) were assessed at baseline and at the end of the study after 6 months.

Results

On heat-stress days, patients showed significantly more symptoms and lower total steps/day compared to thermal comfort days (3,995 ± 2,013 steps/day vs. 5,567 ± 2,434 steps/day, respectively; P < 0.001). There was a significant negative correlation between total steps/day and Temp_max (R = ?0.47; P < 0.001) and humidity (R = ?0.34; P < 0.001). A significant positive correlation was found between daily symptoms and Temp_max (R = +0.79; P < 0.001) and humidity (R = +0.23; P < 0.001).

Conclusions

Heat stress is associated with a compromised clinical status in patients with PAH. Adaptation strategies must be implemented to prevent heart-related morbidity, including therapeutic adjustments and adequate room cooling in the patient’s home and at the hospital.     

Genetic variability of VEGF pathway genes in six randomized phase III trials assessing the addition of bevacizumab to standard therapy

Background

Despite extensive translational research, no validated biomarkers predictive of bevacizumab treatment outcome have been identified.

Methods

We performed a meta-analysis of individual patient data from six randomized phase III trials in colorectal, pancreatic, lung, renal, breast, and gastric cancer to explore the potential relationships between 195 common genetic variants in the vascular endothelial growth factor (VEGF) pathway and bevacizumab treatment outcome.

Results

The analysis included 1,402 patients (716 bevacizumab-treated and 686 placebo-treated). Twenty variants were associated (P < 0.05) with progression-free survival (PFS) in bevacizumab-treated patients. Of these, 4 variants in EPAS1 survived correction for multiple testing (q < 0.05). Genotype-by-treatment interaction tests revealed that, across these 20 variants, 3 variants in VEGF-C (rs12510099), EPAS1 (rs4953344), and IL8RA (rs2234671) were potentially predictive (P < 0.05), but not resistant to multiple testing (q > 0.05). A weak genotype-by-treatment interaction effect was also observed for rs699946 in VEGF-A, whereas Bayesian genewise analysis revealed that genetic variability in VHL was associated with PFS in the bevacizumab arm (q < 0.05). Variants in VEGF-A, EPAS1, and VHL were located in expression quantitative loci derived from lymphoblastoid cell lines, indicating that they affect the expression levels of their respective gene.

Conclusions

This large genetic analysis suggests that variants in VEGF-A, EPAS1, IL8RA, VHL, and VEGF-C have potential value in predicting bevacizumab treatment outcome across tumor types. Although these associations did not survive correction for multiple testing in a genotype-by-interaction analysis, they are among the strongest predictive effects reported to date for genetic variants and bevacizumab efficacy.     

Periprosthetic bone mineral density after total hip arthroplasty with an AMIStem or Quadra femoral component performed by a minimally invasive anterior approach (AMIS): a prospective randomized clinical dual-energy X-ray absorptiometry study

Introduction

This prospective 12 months of dual-energy X-ray absorptiometry (DEXA) study evaluated differences in periprosthetic bone mineral density in 40 patients undergoing cementless total hip arthroplasty (THA) by a minimally invasive anterior approach (AMIS), using Medacta AMIStem or Quadra stems. Both stems are straight rectangular. AMIStem shows reduced lateral flare and length in comparison to Quadra.

Objectives

The main goal of the study is to verify if bone mineral density is equivalent following THA with the AMIStem and Quadra femoral components.

Methods

Forty patients were randomly allocated to the Quadra and AMIStem groups. Three patients were lost to follow-up because they moved to another town, and revision surgery was performed on one patient due to periprosthetic fracture after a car accident. Patients were examined clinically and underwent DEXA preoperatively and at 1 week, 6 weeks, 6 months, and 1 year after THA. Patients enrolled had no preexisting lower limb arthroplasty and no osteoporosis.

Results

Harris hip score increased significantly for Quadra stem 5.3?±?14.1 and AMIStem 41.0?±?13.4. The high-activity hip score increased significantly for Quadra stem 3.8 ±2.2 and AMIStem 4.1?±?2.4. Considering 0.15 mg/cm² as an acceptable difference, bone mineral density for AMIStem and Quadra groups was statistically equivalent. A limited remodeling process with slight bone loss in the proximal calcar region R7, as expected after implantation of uncemented components, was observed for both stems.

Conclusions

The study demonstrates that the two stems are statistically equivalent in all zones at all time points investigated.     

A new mutation in GJC2 associated with subclinical leukodystrophy

Recessive mutations in GJC2, the gene-encoding connexin 47 (Cx47), cause Pelizaeus–Merzbacher-like disease type 1, a severe dysmyelinating disorder. One recessive mutation (p.Ile33Met) has been associated with a much milder phenotype––hereditary spastic paraplegia type 44. Here, we present evidence that a novel Arg98Leu mutation causes an even milder phenotype––a subclinical leukodystrophy. The Arg98Leu mutant forms gap junction plaques in HeLa cells comparable to wild-type Cx47, but electrical coupling was 20-fold lower in cell pairs expressing Arg98Leu than for cell pairs expressing wild-type Cx47. On the other hand, coupling between Cx47Arg98Leu and Cx43WT expressing cells did not show such reductions. Single channel conductance and normalized steady-state junctional conductance–junctional voltage (G _j–V _j) relations differed only slightly from those for wild-type Cx47. Our data suggest that the minimal phenotype in this patient results from a reduced efficiency of opening of Cx47 channels between oligodendrocyte and oligodendrocyte with preserved coupling between oligodendrocyte and astrocyte, and support a partial loss of function model for the mild Cx47 associated disease phenotypes.