Survival analysis of the Wallis interspinous spacer used as an augment to lumbar decompression.

OBJECT: The Wallis fixed interspinous spacer may augment traditional decompression in the treatment of lumbar spinal stenosis. The aim of this study was to determine factors influencing survival of the Wallis interspinous spacer and to identify specific modes and predictors of failure. METHODS: We performed a retrospective cohort study of 244 Wallis interspinous spacers implanted in 195 consecutive patients with a mean age of 56 years (range 21-87) to augment single or multi-level decompression. We examined patient demographics, indications for surgery, surgical techniques and pathology on magnetic resonance imaging (MRI). A Kaplan-Meier survival analysis was performed. RESULTS: Median follow-up was 4.5 years (range 2-8). Sixteen patients were lost to follow-up. Repeat MRI was performed in 98 patients (50%). A recurrent stenosis was found in 21% of patients (41/195) and occurred at a similar incidence at the level of the spacer and at adjacent spinal levels. Revision decompression was performed in 19 patients (10%) at 2.8 ± 1.8 years (range 6 months-6 years) with implant removal in 15 and conversion to fusion in 4 patients. No specific patient factors or pre-operative MRI findings predicted failure. Five-year survival was 91% (95% CI: 79-96%). CONCLUSIONS: The Wallis implant is generally implanted without complication when used as an adjunct to decompression with a good medium term survival. Though disc heights were maintained, the Wallis spacer did not however appear to reduce the incidence of recurrent spinal or foraminal stenosis from that expected from decompression alone.

DNA methylation from germline cells in veterans with PTSD.

In this study we investigated genome-wide sperm DNA methylation patterns in trauma-exposed Vietnam veterans. At the genome-wide level, we identified 3 CpG sites associated with PTSD in sperm including two intergenic and one CpG within the CCDC88C gene. Of those associated with PTSD in sperm at a nominal level, 1868 CpGs were also associated with PTSD in peripheral blood (5.6% overlap) including the RORA, CRHR1 and DOCK2 genes that have been previously implicated in PTSD. A total of 10 CpG sites were significantly associated with a reported history of a diagnosed mental health condition in children and reached genome-wide significance. CpGs associated with a history of a reported mental health condition in children were also enriched (90% of tested genes) for genes previously reported to be resistant to demethylation, making them strong candidates for transgenerational inheritance. In conclusion, our findings identify a unique sperm-specific DNA methylation pattern that is associated with PTSD.

Glucocorticoid receptor polymorphisms and post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is reported in some studies to be associated with increased glucocorticoid (GC) sensitivity. Two common glucocorticoid receptor (GR) polymorphisms (N363S and BclI) appear to contribute to the population variance in GC sensitivity. There is some evidence that there may be a genetic predisposition to PTSD. Hence we studied 118 Vietnam war veterans with PTSD for (i) GR polymorphisms, particularly the N363S and the BclI polymorphisms which are thought to be GC sensitising, and (ii) two measures of GC sensitivity, the low-dose 0.25 mg dexamethasone suppression test (LD-DST) and the dermal vasoconstrictor assay (DVVA). The DST and GR polymorphisms were also performed in 42 combat exposed Vietnam war veterans without PTSD. Basal plasma cortisol levels were not significantly different in PTSD (399.5+/-19.2 nmol/L, N=75) and controls (348.6+/-23.0 nmol/L, N=33) and the LD-DST resulted in similar cortisol suppression in both groups (45.6+/-3.2 vs. 40.8+/-4.1%). The cortisol suppression in PTSD patients does not correlate with Clinician Administered PTSD Scores (CAPS), however there was a significant association between the BclI GG genotype and low basal cortisol levels in PTSD (P=0.048). The response to the DVVA was similar to controls (945+/-122, N=106 vs. 730+/-236, N=28, P=0.42). PTSD patients with the GG genotype, however, tended to be more responsive to DVVA and in this group the DVVA correlated with higher CAPS scores. The only exon 2 GR polymorphisms detected were the R23K and N363S. Heterozygosity for the N363S variant in PTSD, at 5.1% was not more prevalent than in other population studies of the N363S polymorphism in Caucasians (6.0-14.8%). The GG genotype of the BclI polymorphism found to be associated with increased GC sensitivity in many studies showed a tendency towards increased response with DVVA and correlated with higher CAPS scores. In conclusion, the N363S and BclI GR polymorphisms were not more frequent in PTSD patients than controls and reported population frequencies. Our PTSD group did not display GC hypersensitivity, as measured by the LD-DST and DVVA. In a subset of PTSD patients with the BclI GG genotype, CAPS scores and basal cortisol levels were negatively correlated.

The impact of mandatory fortification of flour with folic acid on the blood folate levels of an Australian population.

OBJECTIVE: To determine the impact that mandatory fortification with folic acid of wheat flour used in breadmaking has had on the blood folate levels of an Australian population since it was introduced in September 2009. DESIGN, SETTING AND PATIENTS: A retrospective analysis of serum and red blood cell (RBC) folate levels of 20,592 blood samples collected between April 2007 and April 2010 from a wide variety of inpatients and outpatients and analysed in a large public hospital diagnostic pathology laboratory. MAIN OUTCOME MEASURES: Prevalences of low levels of serum and RBC folate and monthly mean levels before and after introduction of mandatory fortification. RESULTS: Between April 2009 and April 2010, there was a 77% reduction in the prevalence of low serum folate levels (from 9.3% to 2.1%) in all samples tested and an 85% reduction in the prevalence of low RBC folate levels (from 3.4% to 0.5%). In April 2010, the prevalence of low RBC folate levels for females of childbearing age was 0.16% for all samples. There was a 31% increase in mean serum folate level (from 17.7 nmol/L to 23.1 nmol/L; t = 9.3, P < 0.01), and a 22% increase in mean RBC folate level (from 881 nmol/L to 1071 nmol/L). The greatest increment in mean serum folate levels occurred in September 2009, the month that mandatory fortification was introduced, although there was evidence of a gradual change during the preceding months. CONCLUSION: The introduction of mandatory fortification with folic acid has significantly reduced the prevalence of folate deficiency in Australia, including in women of childbearing age.