Epstein-Barr virus infection after adolescence and human herpesvirus 6A as risk factors for multiple sclerosis.

BACKGROUND AND PURPOSE: Infections with human herpesvirus 6A (HHV-6A) and Epstein-Barr virus (EBV) have been linked to multiple sclerosis (MS) development. For EBV, late infection has been proposed as a risk factor, but serological support is lacking. The objective of this study was to investigate how age affects the EBV and HHV-6A associated risks of developing MS. METHODS: In this nested case-control study, Swedish biobanks were accessed to find pre-symptomatically collected blood samples from 670 individuals who later developed relapsing MS and 670 matched controls. A bead-based multiplex assay was used to determine serological response against EBV and HHV-6A. Conditional logistic regression was used to calculate odds ratios and 95% confidence intervals. RESULTS: Seropositivity against EBV exhibited a pattern where associations switched from a decreased risk of developing MS in the group below 20 years of age to an increased risk amongst individuals aged 20-29 and 30-39 years (p for trend 0.020). The age of transition was estimated to be 18.8 years. In contrast, HHV-6A was associated with increased MS risk in all age groups (total cohort odds ratio 2.1, 95% confidence interval 1.6-2.7). CONCLUSIONS: This study suggests EBV infection after adolescence and age independent HHV-6A infection as risk factors for MS.

Prevention of post-dural puncture headache: a randomized controlled trial.

BACKGROUND AND PURPOSE: We investigated 952 subjects undergoing diagnostic lumbar puncture (LP) to study the effects of needle size, needle design and stylet reinsertion on the risk of post-dural puncture headache (PDPH). METHODS: This randomized double-blind study was performed at Umeå University Hospital in Sweden during 2013-2018. Subjects were randomly assigned one of three needles [22 gauge (G) atraumatic, 25G atraumatic and 25G cutting] and stylet reinsertion before needle withdrawal or not. The main outcome measure was PDPH assessed by standardized telephone interview(s) 5 days after the LP, repeated until headache cessation. We used logistic regression to calculate odds ratios (ORs) with 95% confidence intervals (CI) for PDPH. RESULTS: The mean (SD) age was 51.1 (16.7) years and 53.6% were females. The smaller bore (25G) atraumatic needle incurred a lower risk of headache compared with the larger bore (22G) atraumatic needle [22.0% (69/314) vs. 30.2% (98/324); OR, 0.65; 95% CI, 0.45-0.93] and compared with the cutting needle [32.8% (103/314); OR, 0.58; 95% CI, 0.40-0.82]. Reinserting the stylet before needle withdrawal did not reduce the risk of headache. CONCLUSIONS: These data suggest that a 25G atraumatic needle is superior to a larger atraumatic needle, and to a same-sized cutting needle, in preventing PDPH after diagnostic LP. In contrast to one earlier report, this study did not find that stylet reinsertion was effective in preventing PDPH. This study provides class I evidence that a small atraumatic needle decreases the risk of PDPH and that stylet reinsertion does not influence PDPH risk.

Polymorphisms in dopamine-associated genes and cognitive decline in Parkinson's disease.

OBJECTIVES: Cognitive decline is common in Parkinson's disease (PD), but the underlying mechanisms for this complication are incompletely understood. Genotypes affecting dopamine transmission may be of importance. This study investigates whether genotypes associated with reduced prefrontal dopaminergic tone and/or reduced dopamine D2-receptor availability (Catechol-O-methyltransferase [COMT] Val158 Met genotype and DRD2 C957 T genotype) affect the development of cognitive deficits in PD. MATERIALS AND METHODS: One hundred and 34 patients with idiopathic PD, participating in a regional, population-based study of incident parkinsonism, underwent genotyping. After extensive baseline investigations (including imaging and biomarker analyses), the patients were followed prospectively during 6-10 years with neuropsychological evaluations, covering six cognitive domains. Cognitive decline (defined as the incidence of either Parkinson's disease mild cognitive impairment [PD-MCI] or dementia [PDD], diagnosed according to published criteria and blinded to genotype) was studied as the primary outcome. RESULTS: Both genotypes affected cognition, as shown by Cox proportional hazards models. While the COMT 158 Val/Val genotype conferred an increased risk of mild cognitive impairment in patients with normal cognition at baseline (hazard ratio: 2.13, P = .023), the DRD2 957 T/T genotype conferred an overall increased risk of PD dementia (hazard ratio: 3.22, P < .001). The poorer cognitive performance in DRD2 957 T/T carriers with PD occurred mainly in episodic memory and attention. CONCLUSIONS: The results favor the hypothesis that dopamine deficiency in PD not only relate to mild cognitive deficits in frontostriatal functions, but also to a decline in memory and attention. This could indicate that dopamine deficiency impairs a wide network of brain areas.

SUMMER Trial: mesh versus suture repair in small umbilical hernias in adults-a study protocol for a prospective randomized double-blind multicenter clinical trial.

BACKGROUND: Small umbilical hernia repair is one of the most common surgical performances in general surgery. Yet, a gold standard procedure for the repair is still lacking today. There is an increasing evidence that mesh could be advantageous compared to suture repair in lowering recurrence rates. An additional important question remains with regard to the optimal anatomical positioning of the mesh. We hypothesize that the use of an onlay mesh in small umbilical hernia defects can reduce recurrence rates without increasing the complications compared to a simple suture repair. METHODS: A prospective, national, multicenter, randomized, double-blind clinical trial comparing a standardized 4 × 4 cm onlay mesh to a conventional suture repair will be conducted. A total of 288 patients with a primary elective umbilical hernia ≤ 2 cm from 7 participating Swedish surgical centers will be enrolled. Intraoperative randomization will take place using a centralized web-based system resulting in total allocation concealment. Stratification will be done by surgical site and by defect size. Trial participants and follow-up clinical surgeons will be blinded to the assigned allocation. The primary outcome assessed will be postoperative recurrence at 1 and 3 years. Secondary outcomes assessed will be postoperative complications at 30 days and pain 1 year after surgery. DISCUSSION: Currently, there has been no randomized clinical trial comparing the recurrence rates between an onlay mesh repair and a simple suture repair for small umbilical hernia defects. How to best repair a small umbilical hernia continues to be debated. This trial design should allow for a good assessment of the differences in recurrence rate due to the large sample size and the adequate follow-up. Surgeons' concerns surrounding optimal anatomical positioning and fear for larger required dissections are understandable. A small onlay mesh may become an easy and safe method of choice to reduce recurrence rates. Guidelines for small umbilical hernia repairs have stressed the need for reliable data to improve treatment recommendations. We can expect that this trial will have a direct implication on small umbilical hernia repair standards. TRIAL REGISTRATION: ClinicalTrials.gov NCT04231071. Registered on 31 January 2020. SUMMER Trial underwent external peer review as part of the funding process.