Citations

Abstract

Background: Plasma metabolites are associated with cognitive and physical function in the elderly. Because cerebral small vessel disease (SVD) and neurodegeneration are common causes of cognitive and physical function decline, the primary objective of this study was to investigate the associations of six plasma metabolites (two plasma phosphatidylcholines [PCs]: PC aa C36:5 and PC aa 36:6 and four sphingomyelins [SMs]: SM C26:0, SM [OH] C22:1, SM [OH] C22:2, SM [OH] C24:1) with magnetic resonance imaging (MRI) features of cerebral SVD and neurodegeneration in older adults. Methods: This study included 238 older adults in the Atherosclerosis Risk in Communities study at the fifth exam. Multiple linear regression was used to assess the association of each metabolite (log-transformed) in separate models with MRI measures except lacunar infarcts, for which binary logistic regression was used. Results: Higher concentrations of plasma PC aa C36:5 had adverse associations with MRI features of cerebral SVD (odds ratio of 1.69 [95% confidence interval: 1.01, 2.83] with lacunar infarct, and beta of 0.16 log [cm3] [0.02, 0.30] with log [White Matter Hyperintensities (WMH) volume]) while higher concentrations of 3 plasma SM (OH)s were associated with higher total brain volume (beta of 12.0 cm3 [5.5, 18.6], 11.8 cm3 [5.0, 18.6], and 7.3 cm3 [1.2, 13.5] for SM [OH] C22:1, SM [OH] C22:2, and SM [OH] C24:1, respectively). Conclusions: This study identified associations between certain plasma metabolites and brain MRI measures of SVD and neurodegeneration in older adults, particularly higher SM (OH) concentrations with higher total brain volume.

Purpose: The relationship between age-related macular degeneration (AMD) and malignancy, especially cutaneous malignancies, is not well studied. We investigated a possible association between AMD and cutaneous malignancies. Methods: A retrospective, consecutive review of all patients who had received at least 1 intravitreal injection for wet AMD between January 1, 2004, and December 31, 2013, was conducted using the Rochester Epidemiology Project in Olmsted County, Minnesota. Age- and sex-matched control groups included 473 pre–anti–vascular endothelial growth factor era wet AMD patients, 504 concurrent time dry AMD patients, and 504 patients with no AMD. The rates of AMD and overall malignancy, cutaneous malignancies, and specific types of cutaneous malignancies were compared between groups of patients. Results: Patients with wet AMD incurred an increased rate of overall malignancies compared to patients with dry AMD {52.8% wet AMD (confidence interval [CI]: 48.3–57.2) vs. 43.7% dry AMD (CI: 39.3–48.1); P= 0.003} or those without AMD (52.8% wet AMD [CI: 48.3–57.2] vs. 35.3% no AMD [CI: 31.1–39.7]; P = <0.001). Patients with dry AMD also had higher rates of malignancy than those without AMD (43.7% dry AMD [CI: 39.3–48.1] vs. 35.3% no AMD [CI: 31.1–39.7]; P = 0.007). Rate of cutaneous malignancies was increased in patients with wet AMD compared to patients with dry AMD (24.4% wet AMD [CI: 20.7–28.4] vs. 14.6% dry AMD [CI: 11.5–17.9]; P = <0.001) and those with no AMD (24.4% wet AMD [CI: 20.7–28.4] vs. 9.7% no AMD [CI: 7.3–12.7]; P = <0.001). Conclusion and Relevance: To the best of our knowledge, this is the first report to establish an association between AMD and cutaneous malignancies, supporting a possible discussion of the association when a patient presents with one of the two conditions.

Abstract Background Sonicate fluid (SF), a solution derived from vortexing and sonication of explanted cardiovascular implantable electronic devices (CIEDs), is a higher-yield specimen compared with swabs or tissues for culture-based detection of microorganisms associated with CIED infection. Despite this, SF culture fails to identify a causative organism in ~50% of cases. We aimed to evaluate the diagnostic performance of 16S ribosomal RNA gene (rRNA) polymerase chain reaction (PCR)/sequencing of SF and compare it with that of SF culture. Methods We identified 322 SF specimens from extracted CIEDs and reviewed clinical data for each patient. Subjects were classified as having or not having CIED infection. Cases were subcategorized as culture negative if no significant growth was reported from SF cultures and as culture positive if an organism was detected above predefined thresholds. 16S rRNA PCR/sequencing was performed, with the organisms identified reported according to Clinical and Laboratory Standards Institute guidelines for sequence data interpretation. Results A total of 278 SF samples corresponded to infected cases, of which 160 were culture positive and 118 culture negative. The remaining 44 were from noninfected cases, of which 2 were culture positive. Compared with SF culture, the sensitivity of 16S rRNA PCR/sequencing was higher (64% vs 57.5%, P = .003). 16S rRNA PCR/sequencing detected a potential pathogen in 28 of 118 culture-negative cases, identifying staphylococci in the majority (18/28). Conclusions 16S rRNA PCR/sequencing has higher sensitivity to detect bacteria in SF from extracted CIEDs than does SF culture.

Abstract Introduction The South East Asia Research Collaboration in HIV (SEARCH) RV411 clinical trial in Thailand was a systematic investigation of analytic treatment interruption (ATI) in individuals diagnosed and treated since Fiebig stage I acute HIV infection. Here, we explore decision‐making processes and perceptions of trial participation in a phase I trial that raised important ethical considerations, to identify potential areas of improvement in this relatively new field of HIV research. Similar considerations apply to other HIV phase I trials, especially those involving ATI, making this trial a model to identify challenges and opportunities in promoting informed choice. Methods Using longitudinal semi‐structured interviews and a validated questionnaire, we examined how decisions to join or decline the trial were made, whether there was evidence of decisional conflict, and reactions to the trial outcomes. We also explored contrasting views and experiences in this small trial cohort. We report analyses of data from these questionnaires and interviews, conducted from February through December of 2016 with the 14 SEARCH cohort participants who either joined (n = 8) or declined (n = 6) participation in RV411. Results The eight participants and six decliners had low overall decisional conflict, which remained low over time. Decision making was more difficult for decliners than participants, at least initially. While all interviewees described being satisfied with their decisions, our study identified important negative consequences for a few individuals, including seroconversion, negative experiences with optional procedures and disappointment due to rapid viral rebound. Conclusions Although our results reflect the experiences of a small group invited to join this trial, our overall finding of low decisional conflict even while some individuals reported negative experiences provides lessons for clinical trial investigators. We developed points‐to‐consider in helping participants make informed choices, to support participants during the trial and to support decliners in their decisions.

Blood pressure (BP) varies over time within individual patients and across different BP measurement techniques. The effect of different BP targets on the concordance between BP measurements is unknown. The goal of this analysis was to evaluate concordance in: 1) clinic BP and ambulatory BP, 2) clinic visit-to-visit variability and ambulatory BP variability and 3) initial and repeat ambulatory BP. We also sought to evaluate whether treatment assignment of intensive vs standard BP target affected these relationships. The Systolic Blood Pressure Intervention Trial (SPRINT) ambulatory blood pressure monitoring ancillary study obtained ambulatory BP readings in 897 SPRINT participants at the 27 month follow up visit and 203 consecutive repeat ambulatory BP readings taken an average of 9.8 months later. There was poor agreement between clinic systolic BP and daytime ambulatory systolic BP (limits of agreement in Bland-Altman plots of -21 to 34 mm Hg in the intensive treatment group and -26 to 32 mm Hg in the standard treatment group). There was poor agreement between clinic visit-to-visit variability (coefficient of variation) and ambulatory BP variability (coefficient of variation of a 24 hr ambulatory BP) with correlation coefficients for systolic BP <0.16. While there was a high correlation between ambulatory BP at 27 months and repeat ambulatory BP (r ~0.56), there was significant variability between repeat ambulatory BP assessments (limits of agreement of -27 to 21 mm Hg in the intensive group and -23 to 20 mm Hg in the standard group). In conclusion, irrespective of treatment target, we found low concordance in BP and BP variability between clinic BP and ambulatory BP, and additionally between repeat ambulatory BP assessments. These results reinforce the need for multiple guideline adherent BP measurements prior to clinical decision making.