Evaluation of Genetic and Nongenetic Risk Factors for Degenerative Cervical Myelopathy.

STUDY DESIGN: Cohort study. OBJECTIVE: We aimed to evaluate the associations of genetic and nongenetic factors with degenerative cervical myelopathy (DCM). SUMMARY OF BACKGROUND DATA: There is mounting evidence for an inherited predisposition for DCM, but uncertainty remains regarding specific genetic markers involved. Similarly, nongenetic factors are thought to play a role. MATERIALS AND METHODS: Using diagnosis codes from hospital records linked to the UK Biobank cohort, patients with cervical spondylosis were identified followed by the identification of a subset with DCM. Nongenetic variables evaluated included age, sex, race, Townsend deprivation index, body mass index, occupational demands, osteoporosis, and smoking. Genome-wide association analyses were conducted using logistic regression adjusted for age, sex, population principal components, and follow-up. RESULTS: A total of 851 DCM cases out of 2787 cervical spondylosis patients were identified. Several nongenetic factors were independently associated with DCM including age [odds ratio (OR)=1.11, 95% CI=1.01-1.21, P =0.024], male sex (OR=1.63, 95% CI=1.37-1.93, P <0.001), and relative socioeconomic deprivation (OR=1.03, 95% CI=1.00-1.06, P =0.030). Asian race was associated with lower DCM risk (OR=0.44, 95% CI=0.22-0.85, P =0.014). We did not identify genome-wide significant (≤5×10 -8 ) single-nucleotide polymorphisms (SNPs) associated with DCM. The strongest genome-wide signals were at SNP rs67256809 in the intergenic region of the genes LINC02582 and FBXO15 on chromosome 18 ( P =1.12×10 -7 ) and rs577081672 in the GTPBP1 gene on chromosome 22 ( P =2.9×10 -7 ). No SNPs reported in prior DCM studies were significant after adjusting for replication attempts. CONCLUSIONS: Increasing age, male sex, and relative socioeconomic deprivation were identified as independent risk factors for DCM, whereas Asian race was inversely associated. SNPs of potential interest were identified in GTPBP1 and an intergenic region on chromosome 18, but these associations did not reach genome-wide significance. Identification of genetic and nongenetic DCM susceptibility markers may guide understanding of DCM disease processes, inform risk, guide prevention and potentially inform surgical outcomes. LEVEL OF EVIDENCE: Prognostic level III.

Antidepressant Augmentation versus Switch in Treatment-Resistant Geriatric Depression.

BACKGROUND: The benefits and risks of augmenting or switching antidepressants in older adults with treatment-resistant depression have not been extensively studied. METHODS: We conducted a two-step, open-label trial involving adults 60 years of age or older with treatment-resistant depression. In step 1, patients were randomly assigned in a 1:1:1 ratio to augmentation of existing antidepressant medication with aripiprazole, augmentation with bupropion, or a switch from existing antidepressant medication to bupropion. Patients who did not benefit from or were ineligible for step 1 were randomly assigned in step 2 in a 1:1 ratio to augmentation with lithium or a switch to nortriptyline. Each step lasted approximately 10 weeks. The primary outcome was the change from baseline in psychological well-being, assessed with the National Institutes of Health Toolbox Positive Affect and General Life Satisfaction subscales (population mean, 50; higher scores indicate greater well-being). A secondary outcome was remission of depression. RESULTS: In step 1, a total of 619 patients were enrolled; 211 were assigned to aripiprazole augmentation, 206 to bupropion augmentation, and 202 to a switch to bupropion. Well-being scores improved by 4.83 points, 4.33 points, and 2.04 points, respectively. The difference between the aripiprazole-augmentation group and the switch-to-bupropion group was 2.79 points (95% CI, 0.56 to 5.02; P = 0.014, with a prespecified threshold P value of 0.017); the between-group differences were not significant for aripiprazole augmentation versus bupropion augmentation or for bupropion augmentation versus a switch to bupropion. Remission occurred in 28.9% of patients in the aripiprazole-augmentation group, 28.2% in the bupropion-augmentation group, and 19.3% in the switch-to-bupropion group. The rate of falls was highest with bupropion augmentation. In step 2, a total of 248 patients were enrolled; 127 were assigned to lithium augmentation and 121 to a switch to nortriptyline. Well-being scores improved by 3.17 points and 2.18 points, respectively (difference, 0.99; 95% CI, -1.92 to 3.91). Remission occurred in 18.9% of patients in the lithium-augmentation group and 21.5% in the switch-to-nortriptyline group; rates of falling were similar in the two groups. CONCLUSIONS: In older adults with treatment-resistant depression, augmentation of existing antidepressants with aripiprazole improved well-being significantly more over 10 weeks than a switch to bupropion and was associated with a numerically higher incidence of remission. Among patients in whom augmentation or a switch to bupropion failed, changes in well-being and the occurrence of remission with lithium augmentation or a switch to nortriptyline were similar. (Funded by the Patient-Centered Outcomes Research Institute; OPTIMUM ClinicalTrials.gov number, NCT02960763.).

Human Papillomavirus-Associated Sexual Risks Among High School Students in the U.S.: Does Sexual Orientation Play a Role?

We examined the association between sexual orientation and human papillomavirus (HPV)-related risky sexual behaviors among high school students in the U.S. We used the 2015 Youth Risk Behavior Survey, a three-stage cluster sample, nationally representative, cross-sectional study. Participants were sexually active students (Grades 9-12) in public, private, and Catholic schools in 50 states and the District of Columbia (n = 5,958). Sexual orientation dimensions were: sexual self-identity (heterosexual, gay, lesbian, bisexual, and not sure) and sex of sexual contacts. HPV-associated risky sexual risk behaviors selected a priori were early sexual debut (≤ 12 or ≥ 13 years old) and number of lifetime partners (≥ 2 or ≥ 4). Separate multiple logistic regression analyses estimated association between sexual orientation and sex of sexual contacts, and HPV-associated risky sexual behaviors. Among the 5,958 high school students, a quarter had ≥ 4, and two-thirds had ≥ 2 sexual partners. Students who self-identified as bisexual (aOR = 2.43, 99% CI 1.19-4.98) or "not sure" (aOR = 4.56, 99% CI 2.54-8.17) were more likely to have sexual debut before 13 years. Similarly, students whose sexual contacts were adolescent females who had sex with females and males were more likely to have sexual debut before they turned 13 years of age (aOR = 3.46, 99% CI 1.83-6.48), or had ≥ 4 sexual partners (aOR = 2.66, 99% CI 1.74-4.08), or had ≥ 2 sexual partners (aOR = 3.09, 99% CI 1.91-5.00). In conclusion, HPV-associated risky sexual behavior is prevalent among high school students, especially sexual minorities. Interventions tailored to this population could increase HPV vaccine uptake and prevent future HPV-associated cancers and other negative outcomes.

Disparities in human papillomavirus (HPV) vaccine initiation and completion based on sexual orientation among women in the United States.

OBJECTIVES: We compared HPV vaccine initiation and completion of heterosexual with lesbian and bisexual (LB) women. METHODS: We aggregated National Health and Nutrition Examination Survey data from 2009 to 2016 for 3,017 women aged 18 to 34 y in the United States. HPV vaccine initiation was defined as reported receipt of ≥1 dose of the vaccine and completion as receipt of the three recommended doses. Weighted percentages and multivariable logistic regression models were used to examine differences in HPV vaccine initiation and completion between heterosexual and LB women. RESULTS: Approximately 12% of respondents self-identified as LB women. Overall, a higher percentage of respondents (26%) had initiated the HPV vaccine than completed the three vaccine doses (17%). In the bivariate analysis, LB women had higher initiation ([35% of LB women versus 25% heterosexual]; p = .0012) and completion rates ([24% of LB women versus 17% heterosexual]; p = .0052) than heterosexual women. After adjusting for covariates, compared to heterosexual women, LB women were 60% (aOR = 1.60, 95% CI: 1.16-2.19) more likely to initiate and 63% (aOR = 1.63, 95% CI: 1.12-2.37) more likely to complete the HPV vaccine. CONCLUSIONS: Although LB women had higher likelihood of HPV vaccine initiation and completion compared with heterosexual women, their HPV vaccine uptake was well below the Healthy People 2020 target (80%). Understanding differences in the drivers of vaccine uptake in the LB population may inform strategies that would further increase HPV vaccine uptake toward achieving the 80% completion target.

"Race for the Surface": Eukaryotic Cells Can Win.

With an aging population and the consequent increasing use of medical implants, managing the possible infections arising from implant surgery remains a global challenge. Here, we demonstrate for the first time that a precise nanotopology provides an effective intervention in bacterial cocolonization enabling the proliferation of eukaryotic cells on a substratum surface, preinfected by both live Gram-negative, Pseudomonas aeruginosa, and Gram-positive, Staphylococcus aureus, pathogenic bacteria. The topology of the model black silicon (bSi) substratum not only favors the proliferation of eukaryotic cells but is biocompatible, not triggering an inflammatory response in the host. The attachment behavior and development of filopodia when COS-7 fibroblast cells are placed in contact with the bSi surface are demonstrated in the dynamic study, which is based on the use of real-time sequential confocal imaging. Bactericidal nanotopology may enhance the prospect for further development of inherently responsive antibacterial nanomaterials for bionic applications such as prosthetics and implants.