Genetic variation in the HLA region is associated with susceptibility to herpes zoster.

Herpes zoster, commonly referred to as shingles, is caused by the varicella zoster virus (VZV). VZV initially manifests as chicken pox, most commonly in childhood, can remain asymptomatically latent in nerve tissues for many years and often re-emerges as shingles. Although reactivation may be related to immune suppression, aging and female sex, most inter-individual variability in re-emergence risk has not been explained to date. We performed a genome-wide association analyses in 22,981 participants (2280 shingles cases) from the electronic Medical Records and Genomics Network. Using Cox survival and logistic regression, we identified a genomic region in the combined and European ancestry groups that has an age of onset effect reaching genome-wide significance (P>1.0 × 10(-8)). This region tags the non-coding gene HCP5 (HLA Complex P5) in the major histocompatibility complex. This gene is an endogenous retrovirus and likely influences viral activity through regulatory functions. Variants in this genetic region are known to be associated with delay in development of AIDS in people infected by HIV. Our study provides further suggestion that this region may have a critical role in viral suppression and could potentially harbor a clinically actionable variant for the shingles vaccine.

Local Anesthesia with Bupivacaine and Lidocaine for Vertebral Fracture trial (LABEL): a report of outcomes and comparison with the Investigational Vertebroplasty Efficacy and Safety Trial (INVEST).

BACKGROUND AND PURPOSE: INVEST is a recently published double-blind placebo controlled randomized trial that demonstrated similar improvements in pain between blinded vertebroplasty and sham-vertebroplasty groups. LABEL is a trial determining the efficacy of pain relief of an injection of lidocaine and bupivacaine at the site of painful osteoporotic vertebral compression fractures in unblinded patients. We compared outcomes from the unblinded LABEL trial with those of blinded control patients from the lead site of the INVEST, exploring the role of blinding on the benefit of local anesthesia infusion for painful vertebral compression fractures. MATERIALS AND METHODS: Nineteen patients with painful osteoporotic vertebral compression fractures underwent unblinded injection of lidocaine and bupivacaine at the site of painful osteoporotic vertebral compression fractures. Patients were given the option of undergoing vertebroplasty at any time following the procedure. Primary outcome measures were change in the RDQ and pain (at rest, with activity, and average 24-hour pain) at days 1 and 3 following the injection. Day 3 change in RDQ scores and change in average 24-hour pain were compared for LABEL and INVEST control patients from the lead site (n = 16). RESULTS: Among patients in the LABEL trial, we detected no significant improvement in RDQ scores, pain at rest, and average 24-hour pain at days 1 and 3, whereas pain with activity improved significantly at both time points. INVEST control patients from the lead site experienced significantly greater improvement in average pain during 24 hours at days 1 (P = .03) and 3 (P = .04) and significantly greater improvements in RDQ scores at day 3 (P = .006) than patients from LABEL. CONCLUSIONS: An unblinded injection of local anesthesia is ineffective in treating pain from osteoporotic compression fractures. This suggests that factors other than local anesthesia were responsible for the observed improvement in the control group in INVEST.

Baseline pain and disability in the Investigational Vertebroplasty Efficacy and Safety Trial.

BACKGROUND AND PURPOSE: Multiple case series of vertebroplasty outcomes have been published, though no large, placebo controlled trial has yet been performed. Our aim was to report baseline characteristics for the Investigational Vertebroplasty Efficacy and Safety Trial (INVEST), a randomized blinded controlled study of vertebroplasty. MATERIALS AND METHODS: We compared baseline demographics, pain scores, and scores on the modified Roland-Morris Disability Scale (RMDS), a back pain-specific metric, between 2 groups. One group included subjects enrolled at the lead INVEST site (n = 27 to date). The second group consisted of eligible patients seen concurrently at the lead INVEST site, who declined enrollment (n = 70). Comparisons were made by using 2-sample t tests. RESULTS: Mean ages were similar between groups, averaging approximately 74 years among study participants and 77 years among nonenrolled eligible patients (P = .17). Approximately 75% of subjects were female in both groups. RMDS scores of enrolled patients at the lead site (18.0 +/- 4.2) were not statistically different from those of eligible nonenrolled patients at the lead site (18.6 +/- 3.6, P = .49). Pain scores in the enrolled subjects were measured as "average intensity over the prior 24 hours" with mean scores of 7.6 +/- 2.1 among enrolled patients at the lead site. Pain scores in eligible nonenrolled patients were measured as "pain at rest," with mean score of 3.4 +/- 3.3, and "pain with activity," with mean score of 8.5 +/- 2.0. CONCLUSIONS: Patient demographics among subjects enrolled in the INVEST are similar to those in a cohort of eligible nonenrolled patients. Back pain-specific disability was similar between subjects enrolled in the INVEST study and eligible nonenrolled patients at the lead site.