Impact of Non-HIV Related Comorbidities on Retention in HIV Medical Care: Does Retention Improve Over Time?

The purpose of this study was to understand how the presence of comorbid conditions affects retention in HIV medical care over time. A retrospective cohort design employing a medical chart review was conducted. A generalized linear mixed model was used to determine the predictors that affect retention over time. The mean follow-up for the study population was 5.75 years, and only 48.6 % achieved optimal retention. During the study period, 882 non-HIV related comorbidities were diagnosed in 610 (44.9 %) patients of whom, approximately 31 % had ≥2 comorbidities diagnosed. In the mixed model, the number of comorbidities diagnosed during the study period was associated with improved retention over time (odds ratio = 2.28; 95 % confidence interval = 1.83–2.71). Having a non-HIV related comorbid condition was associated with improved retention, while those patients who were ‘healthier’ had worse retention. More research is needed to identify factors that improve retention and to quantify the impact of these factors.     

Position statement on opportunistic genomic screening from the Association of Genetic Nurses and Counsellors (UK and Ireland)

The American College of Medical Genetics and Genomics released recommendations for reporting incidental findings (IFs) in clinical exome and genome sequencing. These suggest ‘opportunistic genomic screening'' should be available to both adults and children each time a sequence is done and would be undertaken without seeking preferences from the patient first. Should opportunistic genomic screening be implemented in the United Kingdom, the Association of Genetic Nurses and Counsellors (AGNC), which represents British and Irish genetic counsellors and nurses, feels strongly that the following must be considered (see article for complete list): (1) Following appropriate genetic counselling, patients should be allowed to consent to or opt out of opportunistic genomic screening. (2) If true IFs are discovered the AGNC are guided by the report from the Joint Committee on Medical Genetics about the sharing of genetic testing results. (3) Children should not be routinely tested for adult-onset conditions. (4) The formation of a list of variants should involve a representative from the AGNC as well as a patient support group. (5) The variants should be for serious or life-threatening conditions for which there are treatments or preventative strategies available. (6) There needs to be robust evidence that the benefits of opportunistic screening outweigh the potential harms. (7) The clinical validity and utility of variants should be known. (8) There must be a quality assurance framework that operates to International standards for laboratory testing. (9) Psychosocial research is urgently needed in this area to understand the impact on patients.     

Trajectory Clustering of Estradiol and Follicle-Stimulating Hormone during the Menopausal Transition among Women in the Study of Women's Health across the Nation (SWAN)

Context: Variability in the pattern of change in estradiol (E2) and FSH levels over the menopause transition has not been well defined. Objective: The current study aimed to determine whether different trajectories of E2 and FSH could be identified and whether race/ethnicity and body mass index were related to the different trajectories. Design: The Study of Women's Health Across the Nation is a longitudinal observational study of the menopausal transition. Setting: Women aged 42-52 yr from seven participating sites were recruited and underwent up to 11 annual visits. Participants: Postmenopausal women with 12 or more months of amenorrhea that was not due to hysterectomy/oophorectomy and who were not using hormone therapy before the final menstrual period participated in the study. Main Outcome Measures: Annual serum E2 and FSH levels anchored to final menstrual period were measured. Results: Four distinct E2 trajectories and three distinct FSH trajectories were identified. The E2 trajectories were: slow decline (26.9%), flat (28.6%), rise/slow decline (13.1%), and rise/steep decline (31.5%). The FSH trajectories were: low (10.6%), medium (48.7%), and high (41.7%) rising patterns. Obesity increased the likelihood of a flat E2 and low FSH trajectory for all race/ethnic groups. Normal-weight Caucasian and African-American women tended to follow the rise/steep decline E2 and high FSH trajectories. Normal-weight Chinese/Japanese women tended to follow the slow decline E2 and the high/medium FSH trajectories. Conclusions: E2 and FSH trajectories over the menopausal transition are not uniform across the population of women. Race/ethnicity and body mass index affect the trajectory of both E2 and FSH change over the menopausal transition.     

Unifying the spatial epidemiology and molecular evolution of emerging epidemics

We introduce a conceptual bridge between the previously unlinked fields of phylogenetics and mathematical spatial ecology, which enables the spatial parameters of an emerging epidemic to be directly estimated from sampled pathogen genome sequences. By using phylogenetic history to correct for spatial autocorrelation, we illustrate how a fundamental spatial variable, the diffusion coefficient, can be estimated using robust nonparametric statistics, and how heterogeneity in dispersal can be readily quantified. We apply this framework to the spread of the West Nile virus across North America, an important recent instance of spatial invasion by an emerging infectious disease. We demonstrate that the dispersal of West Nile virus is greater and far more variable than previously measured, such that its dissemination was critically determined by rare, long-range movements that are unlikely to be discerned during field observations. Our results indicate that, by ignoring this heterogeneity, previous models of the epidemic have substantially overestimated its basic reproductive number. More generally, our approach demonstrates that easily obtainable genetic data can be used to measure the spatial dynamics of natural populations that are otherwise difficult or costly to quantify.     

T-cell receptor (TCR) interaction with peptides that mimic nickel offers insight into nickel contact allergy

T cell-mediated allergy to Ni⁺⁺ is one of the most common forms of allergic contact dermatitis, but how the T-cell receptor (TCR) recognizes Ni⁺⁺ is unknown. We studied a TCR from an allergic patient that recognizes Ni⁺⁺ bound to the MHCII molecule DR52c containing an unknown self-peptide. We identified mimotope peptides that can replace both the self-peptide and Ni⁺⁺ in this ligand. They share a p7 lysine whose εNH₂ group is surface-exposed when bound to DR52c. Whereas the TCR uses germ-line complementary-determining region (CDR)1/2 amino acids to dock in the conventional diagonal mode on the mimotope–DR52c complex, the interface is dominated by the TCR Vβ CDR3 interaction with the p7 lysine. Mutations in the TCR CDR loops have similar effects on the T-cell response to either the mimotope or Ni⁺⁺ ligand. We suggest that the mimotope p7 lysine mimics Ni⁺⁺ in the natural TCR ligand and that MHCII β-chain flexibility in the area around the peptide p7 position forms a common site for cation binding in metal allergies.