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Importance: Late-onset Alzheimer disease (AD) is highly heritable. Genome-wide association studies have identified more than 20 AD risk genes. The precise mechanism through which many of these genes are associated with AD remains unknown., Objective: To investigate the association of the top 20 AD risk variants with brain amyloidosis., Design, Setting, and Participants: This study analyzed the genetic and florbetapir F 18 data from 322 cognitively normal control individuals, 496 individuals with mild cognitive impairment, and 159 individuals with AD dementia who had genome-wide association studies and 18F-florbetapir positron emission tomographic data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), a prospective, observational, multisite tertiary center clinical and biomarker study. This ongoing study began in 2005., Main Outcomes and Measures: The study tested the association of AD risk allele carrier status (exposure) with florbetapir mean standard uptake value ratio (outcome) using stepwise multivariable linear regression while controlling for age, sex, and apolipoprotein E ε4 genotype. The study also reports on an exploratory 3-dimensional stepwise regression model using an unbiased voxelwise approach in Statistical Parametric Mapping 8 with cluster and significance thresholds at 50 voxels and uncorrected P < .01., Results: This study included 977 participants (mean [SD] age, 74 [7.5] years; 535 [54.8%] male and 442 [45.2%] female) from the ADNI-1, ADNI-2, and ADNI-Grand Opportunity. The adenosine triphosphate-binding cassette subfamily A member 7 (ABCA7) gene had the strongest association with amyloid deposition (χ2 = 8.38, false discovery rate-corrected P < .001), after apolioprotein E ε4. Significant associations were found between ABCA7 in the asymptomatic and early symptomatic disease stages, suggesting an association with rapid amyloid accumulation. The fermitin family homolog 2 (FERMT2) gene had a stage-dependent association with brain amyloidosis (FERMT2 × diagnosis χ2 = 3.53, false discovery rate-corrected P = .05), which was most pronounced in the mild cognitive impairment stage., Conclusions and Relevance: This study found an association of several AD risk variants with brain amyloidosis. The data also suggest that AD genes might differentially regulate AD pathologic findings across the disease stages.

Importance: Laparoscopic ventral hernia repair (LVHR) using mesh is a well-established intervention for ventral hernia, but pain control can be challenging., Objective: To determine whether instillation of a long-acting local anesthetic between the mesh and the peritoneum after LVHR reduces pain or narcotic requirements., Design, Setting, and Participants: A prospective, double-blind, randomized clinical trial with data collection during a brief hospital stay in a tertiary care, community teaching hospital over 3 years between December 15, 2011, and March 28, 2014. Of 120 screened patients undergoing LVHR in this intention-to-treat analysis, 99 eligible patients were randomized. Forty-two patients received the study drug, and 38 patients received placebo. Patients with a history of chronic narcotic use were excluded., Intervention: After mesh placement, a long-acting local anesthetic (bupivacaine hydrochloride, 0.50%) or placebo (0.9% normal saline) was injected between the mesh and the peritoneum., Main Outcomes and Measures: Postoperative pain (on a standard scale ranging from 0 to 10), and narcotic medication use (intravenous morphine equivalents). There were no adverse events., Results: Baseline and operative characteristics were similar except that the treatment group was older (61.8 vs 52.3 years, P = .001). After surgery, pain scores in the recovery room (3.2 vs 4.7, P = .003), interval total narcotic use (6.7 vs 12.5 mg, P = .003 at <4 hours and 0 vs 2.7 mg, P = .01 at 8-12 hours), and total intravenous narcotic use (9.2 vs 17.2 mg of morphine sulfate equivalents, P = .03) were significantly less in the treatment group., Conclusions and Relevance: Administration of a long-acting local anesthetic between the mesh and the peritoneum significantly reduces postoperative pain and narcotic use after LVHR., Trial Registration: clinicaltrials.gov Identifier: NCT01530815.