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  • 1
    Online Resource
    Online Resource
    Association of Ultra-Widefield Fluorescein Angiography–Identified Retinal Nonperfusion and the Risk of Diabetic Retinopathy Worsening Over Time
    American Medical Association (AMA) ; 2022
    In:  JAMA Ophthalmology Vol. 140, No. 10 ( 2022-10-01), p. 936-
    Details
    In: JAMA Ophthalmology, American Medical Association (AMA), Vol. 140, No. 10 ( 2022-10-01), p. 936-
    Abstract: Presence of predominantly peripheral diabetic retinopathy (DR) lesions on ultra-widefield fluorescein angiography (UWF-FA) was associated with greater risk of DR worsening or treatment over 4 years. Whether baseline retinal nonperfusion assessment is additionally predictive of DR disease worsening is unclear. Objective To assess whether the extent and location of retinal nonperfusion identified on UWF-FA are associated with worsening in Diabetic Retinopathy Severity Scale (DRSS) score or DR treatment over time. Design, Setting, and Participants This cohort study was a prospective, multicenter, longitudinal observational study with data for 508 eyes with nonproliferative DR and gradable nonperfusion on UWF-FA at baseline. All images were graded at a centralized reading center; 200° ultra-widefield (UWF) color images were graded for DR at baseline and annually for 4 years. Baseline 200° UWF-FA images were graded for nonperfused area, nonperfusion index (NPI), and presence of predominantly peripheral lesions on UWF-FA (FA PPL). Interventions Treatment of DR or diabetic macular edema was at investigator discretion. Main Outcomes and Measures Association of baseline UWF-FA nonperfusion extent with disease worsening, defined as either 2 or more steps of DRSS worsening within Early Treatment Diabetic Retinopathy Study fields on UWF-color images or receipt of DR treatment. Results After adjusting for baseline DRSS, the risk of disease worsening over 4 years was higher in eyes with greater overall NPI (hazard ratio [HR] for 0.1-unit increase, 1.11; 95% CI, 1.02-1.21; P  = .02) and NPI within the posterior pole (HR for 0.1-unit increase, 1.35; 95% CI, 1.17-1.56; P   & amp;lt; .001) and midperiphery (HR for 0.1-unit increase, 1.08; 95% CI, 1.00-1.16; P  = .04). In a multivariable analysis adjusting for baseline DRSS score and baseline systemic risk factors, greater NPI (HR, 1.11; 95% CI, 1.02-1.22; P  = .02) and presence of FA PPL (HR, 1.89; 95% CI, 1.35-2.65; P   & amp;lt; .001) remained associated with disease worsening. Conclusions and Relevance This 4-year longitudinal study has demonstrated that both greater baseline retinal nonperfusion and FA PPL on UWF-FA are associated with higher risk of disease worsening, even after adjusting for baseline DRSS score and known systemic risk. These associations between disease worsening and retinal nonperfusion and FA PPL support the increased use of UWF-FA to complement color fundus photography in future efforts for DR prognosis, clinical care, and research.
    Type of Medium: Online Resource
    ISSN: 2168-6165
    URL: Article
    DOI: 10.1001/jamaophthalmol.2022.3130
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2022
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  • 2
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    Association of Predominantly Peripheral Lesions on Ultra-Widefield Imaging and the Risk of Diabetic Retinopathy Worsening Over Time
    American Medical Association (AMA) ; 2022
    In:  JAMA Ophthalmology Vol. 140, No. 10 ( 2022-10-01), p. 946-
    Details
    In: JAMA Ophthalmology, American Medical Association (AMA), Vol. 140, No. 10 ( 2022-10-01), p. 946-
    Abstract: Ultra-widefield (UWF) imaging improves the ability to identify peripheral diabetic retinopathy (DR) lesions compared with standard imaging. Whether detection of predominantly peripheral lesions (PPLs) better predicts rates of disease worsening over time is unknown. Objective To determine whether PPLs identified on UWF imaging are associated with increased disease worsening beyond the risk associated with baseline Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) score. Design, Setting, and Participants This cohort study was a prospective, multicenter, longitudinal observational study conducted at 37 US and Canadian sites with 388 participants enrolled between February and December 2015. At baseline and annually through 4 years, 200° UWF-color images were obtained and graded for DRSS at a reading center. Baseline UWF-color and UWF-fluorescein angiography (FA) images were evaluated for the presence of PPL. Data were analyzed from May 2020 to June 2022. Interventions Treatment of DR or diabetic macular edema was at investigator discretion. Main Outcomes and Measures Predominantly peripheral lesions were defined as DR lesions with a greater extent outside vs inside the 7 standard ETDRS fields. Primary outcome was disease worsening defined as worsening 2 steps or more on the DRSS or receipt of DR treatment. Analyses were adjusted for baseline DRSS score and correlation between 2 study eyes of the same participant. Results Data for 544 study eyes with nonproliferative DR (NPDR) were analyzed (182 [50%] female participants; median age, 62 years; 68% White). The 4-year disease worsening rates were 45% for eyes with baseline mild NPDR, 40% for moderate NPDR, 26% for moderately severe NPDR, and 43% for severe NPDR. Disease worsening was not associated with color PPL at baseline (present vs absent: 38% vs 43%; HR, 0.78; 95% CI, 0.57-1.08; P  = .13) but was associated with FA PPL at baseline (present vs absent: 50% vs 31%; HR, 1.72; 95% CI, 1.25-2.36; P   & amp;lt; .001). Conclusions and Relevance Although no association was identified with color PPL, presence of FA PPL was associated with greater risk of disease worsening over 4 years, independent of baseline DRSS score. These results suggest that use of UWF-FA to evaluate retinas peripheral to standard ETDRS fields may improve the ability to predict disease worsening in NPDR eyes. These findings support use of UWF-FA for future DR staging systems and clinical care to more accurately determine prognosis in NPDR eyes.
    Type of Medium: Online Resource
    ISSN: 2168-6165
    URL: Article
    DOI: 10.1001/jamaophthalmol.2022.3131
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2022
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  • 3
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    Four-Year Visual Outcomes in the Protocol W Randomized Trial of Intravitreous Aflibercept for Prevention of Vision-Threatening Complications of Diabetic Retinopathy
    American Medical Association (AMA) ; 2023
    In:  JAMA Vol. 329, No. 5 ( 2023-02-07), p. 376-
    Details
    In: JAMA, American Medical Association (AMA), Vol. 329, No. 5 ( 2023-02-07), p. 376-
    Abstract: Anti–vascular endothelial growth factor (VEGF) injections in eyes with nonproliferative diabetic retinopathy (NPDR) without center-involved diabetic macular edema (CI-DME) reduce development of vision-threatening complications from diabetes over at least 2 years, but whether this treatment has a longer-term benefit on visual acuity is unknown. Objective To compare the primary 4-year outcomes of visual acuity and rates of vision-threatening complications in eyes with moderate to severe NPDR treated with intravitreal aflibercept compared with sham. The primary 2-year analysis of this study has been reported. Design, Setting, and Participants Randomized clinical trial conducted at 64 clinical sites in the US and Canada from January 2016 to March 2018, enrolling 328 adults (399 eyes) with moderate to severe NPDR (Early Treatment Diabetic Retinopathy Study [ETDRS] severity level 43-53) without CI-DME. Interventions Eyes were randomly assigned to 2.0 mg aflibercept (n = 200) or sham (n = 199). Eight injections were administered at defined intervals through 2 years, continuing quarterly through 4 years unless the eye improved to mild NPDR or better. Aflibercept was given in both groups to treat development of high-risk proliferative diabetic retinopathy (PDR) or CI-DME with vision loss. Main Outcomes and Measures Development of PDR or CI-DME with vision loss (≥10 letters at 1 visit or ≥5 letters at 2 consecutive visits) and change in visual acuity (best corrected ETDRS letter score) from baseline to 4 years. Results Among participants (mean age 56 years; 42.4% female; 5% Asian, 15% Black, 32% Hispanic, 45% White), the 4-year cumulative probability of developing PDR or CI-DME with vision loss was 33.9% with aflibercept vs 56.9% with sham (adjusted hazard ratio, 0.40 [97.5% CI, 0.28 to 0.57] ; P   & amp;lt; .001). The mean (SD) change in visual acuity from baseline to 4 years was −2.7 (6.5) letters with aflibercept and −2.4 (5.8) letters with sham (adjusted mean difference, −0.5 letters [97.5% CI, −2.3 to 1.3]; P  = .52). Antiplatelet Trialists’ Collaboration cardiovascular/cerebrovascular event rates were 9.9% (7 of 71) in bilateral participants, 10.9% (14 of 129) in unilateral aflibercept participants, and 7.8% (10 of 128) in unilateral sham participants. Conclusions and Relevance Among patients with NPDR but without CI-DME, at 4 years treatment with aflibercept vs sham, initiating aflibercept treatment only if vision-threatening complications developed, resulted in statistically significant anatomic improvement but no improvement in visual acuity. Aflibercept as a preventive strategy, as used in this trial, may not be generally warranted for patients with NPDR without CI-DME. Trial Registration ClinicalTrials.gov Identifier: NCT02634333
    Type of Medium: Online Resource
    ISSN: 0098-7484
    URL: Article
    DOI: 10.1001/jama.2022.25029
    RVK:
    XA 10000
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2023
    detail.hit.zdb_id: 2958-0
    detail.hit.zdb_id: 2018410-4
    SSG: 5,21
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  • 4
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    Syndemics and preexposure prophylaxis are independently associated with rectal immune dysregulation in sexual minority men
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  AIDS Vol. 35, No. 8 ( 2021-07-1), p. 1295-1300
    Details
    In: AIDS, Ovid Technologies (Wolters Kluwer Health), Vol. 35, No. 8 ( 2021-07-1), p. 1295-1300
    Abstract: Syndemic conditions have been linked to engagement in receptive condomless anal sex (CAS) and HIV seroconversion. However, little is known about the biological pathways whereby syndemics could amplify vulnerability to HIV and other sexually transmitted infections (STIs). Design: HIV-negative sexual minority men (i.e. gay, bisexual and other MSM) were recruited from four STI clinics in South Florida for a cross-sectional study. Methods: Participants completed assessments for four syndemic conditions: depression, posttraumatic stress disorder, hazardous alcohol use and any stimulant use (i.e. any self-reported use or reactive urine toxicology results). Cytokine and chemokine levels were measured using LEGENDplex from the rectal swabs of 92 participants reporting receptive CAS and no antibiotic use in the past three months. Results: After controlling for age, race/ethnicity, preexposure prophylaxis (PrEP) use and number of receptive CAS partners, a greater number of syndemic conditions was associated with higher levels of rectal cytokines/chemokines relevant to immune activation, inflammation and the expansion and maintenance of T-helper 17 target cells, including rectal interferon-gamma (β = 0.22; P  = 0.047), CXCL-8 (β = 0.24; P  = 0.025) and interleukin-23 (β = 0.22; P  = 0.049). Elevations in rectal cytokine or chemokine levels were most pronounced among participants experiencing two or more syndemic conditions compared with those experiencing no syndemic conditions. PrEP use was independently associated with elevations in multiple rectal cytokines/chemokines. Conclusion: Syndemic conditions could increase biological vulnerability to HIV and other STIs in sexual minority men by potentiating rectal immune dysregulation.
    Type of Medium: Online Resource
    ISSN: 0269-9370 , 1473-5571
    URL: Article
    DOI: 10.1097/QAD.0000000000002866
    RVK:
    XA 16838
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 2012212-3
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  • 5
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    Novelty Seeking as a Phenotypic Marker of Adolescent Substance Use
    SAGE Publications ; 2015
    In:  Substance Abuse: Research and Treatment Vol. 9s1 ( 2015-01), p. SART.S22440-
    Details
    In: Substance Abuse: Research and Treatment, SAGE Publications, Vol. 9s1 ( 2015-01), p. SART.S22440-
    Abstract: Trait novelty seeking has been consistently implicated in substance use, yet the origins and mechanisms of novelty seeking in substance use proneness are unclear. We aimed to characterize novelty seeking as a phenotypic marker of substance use proneness in adolescence, a critical period for drug use experimentation. To this end, we parsed novelty seeking's two constituent subdimensions – exploratory excitability (drive for novel experience) and impulsiveness (careless decision-making) – and explored the individual relations of these dimensions to: (1) the use of a variety of licit and illicit substances, (2) family history of substance use, and (3) subjective drug effects. Five hundred eighty five adolescents (mean age = 14.5 years) completed surveys of key variables. Results indicated that, when accounting for the covariation among exploratory excitability and impulsiveness, impulsiveness emerged as the more salient correlate of substance use and was independently associated with initiation of nearly all drug classes. Mediation analyses of the mechanisms of novelty seeking-related risk illustrated that impulsiveness mediated the association of family history of substance use with both initiation and past 30-day frequency of use. Both impulsiveness and exploratory excitability were associated with increased positive and negative subjective drug effects, and the analyses supported a significant indirect pathway from impulsiveness to a more frequent use via positive subjective effects. Although limited by a cross-sectional design, these findings suggest that impulsiveness-like aspects of the novelty seeking construct may represent a useful phenotypic marker for early substance use proneness that potentially (1) increases initiation risk, (2) has familial origins, and (3) promotes more frequent use by altering subjective drug response.
    Type of Medium: Online Resource
    ISSN: 1178-2218 , 1178-2218
    URL: Article
    DOI: 10.4137/SART.S22440
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2015
    detail.hit.zdb_id: 2517768-0
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  • 6
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    Pathways and Intersections: Multifaceted Approaches to Engage Individuals From Underrepresented and Marginalized Communities in HIV Research and Career Development
    Ovid Technologies (Wolters Kluwer Health) ; 2023
    In:  JAIDS Journal of Acquired Immune Deficiency Syndromes Vol. 94, No. 2S ( 2023-10-1), p. S116-S121
    Details
    In: JAIDS Journal of Acquired Immune Deficiency Syndromes, Ovid Technologies (Wolters Kluwer Health), Vol. 94, No. 2S ( 2023-10-1), p. S116-S121
    Abstract: The underrepresentation of historically marginalized groups in the HIV research workforce is a barrier to reaching national Ending the Epidemic goals. Setting: The Harvard University Center for AIDS Research (HU CFAR) Diversity Equity and Inclusion Working Group (DEI WG) uses a multifaceted approach to enhance the field's diversity. Methods: We established a DEI WG to improve the recruitment, inclusion, and retention of underrepresented minorities (URMs) in HIV research. We use community-based, participatory processes to establish and expand education and outreach programs about HIV care and research to better connect the HU CFAR to communities affected by HIV. This article reports on the development of the WG in July 2022, progress in its first year, and future plans. Results: We have built a network of 〉 50 investigators across the university for monthly meetings; partnered with existing research pathway programs for high school, undergraduate, and graduate students, directly supporting 7 new trainees and linking CFAR investigators to additional mentorship opportunities; and created 2-year Scholar Awards for 5 URM investigators in HIV. Planned work includes needs assessments for early-stage investigators to understand factors contributing to inclusion and retention and new pathway and outreach programming being developed with community partner minority-serving institutions. Conclusions: The HU CFAR DEI WG strives to ensure that individuals from underrepresented, marginalized, and minoritized communities have an opportunity to contribute to HIV research and that research is informed by the needs of the communities affected by the epidemic. An intersectional approach should be incorporated into HIV research pathway initiatives.
    Type of Medium: Online Resource
    ISSN: 1525-4135
    URL: Article
    DOI: 10.1097/QAI.0000000000003265
    RVK:
    XA 10000
    RVK:
    XA 51942
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 2038673-4
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  • 7
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    Attitudes towards participating in research involving digital pill systems to measure oral HIV pre-exposure chemoprophylaxis: a cross-sectional study among men who have sex with men with substance use in the USA
    BMJ ; 2023
    In:  BMJ Open Vol. 13, No. 1 ( 2023-01), p. e067549-
    Details
    In: BMJ Open, BMJ, Vol. 13, No. 1 ( 2023-01), p. e067549-
    Abstract: This quantitative survey sought to understand, among men who have sex with men (MSM) with potentially problematic substance use, the attitudes towards participation in research involving digital pill systems (DPS) for HIV pre-exposure prophylaxis (PrEP) adherence measurement, and the barriers and facilitators to research participation. Design One-time, cross-sectional, online sampling-based survey. Setting US social networking app predominantly focused on MSM. Participants MSM without HIV who reported current use of oral PrEP, potentially problematic substance use and sexual activity in the past 3 months. A total of 157 participants were eligible, passed validity checks and enrolled. Outcome measures Perceptions of DPS usefulness, accuracy and usability (System Usability Scale (SUS)); willingness and motivations to participate in DPS research; preferences for access to and feedback on DPS adherence data; data sharing considerations; and medical mistrust (Group-Based Medical Mistrust Scale (GBMMS)). Results Most of the sample (N=157) was white (n=119, 75.8%), gay (n=124, 79.0%) and cisgender (n=150, 95.5%). The median age was 33 years (IQR: 14). The mean GBMMS score was 13.5 (SD=5.2), and the median SUS score was 70 (IQR: 27.5). In the past 3 months, 36.3% (n=57) reported frequent use of substances before or during sex, and 62.4% (n=98) engaged in condomless sex. While most were adherent to PrEP, approximately 34.4% (n=54) expressed significant worry about daily adherence. Participants wished to monitor their PrEP adherence daily (n=66, 42.0%) and 52% (n=82) were very willing to participate in DPS-based research. The majority were minimally concerned about sharing DPS-detected adherence data with research teams (n=126, 80.3%), and were extremely willing to share these data with healthcare providers (n=109, 69.4%). Conclusions In this sample, MSM without HIV who use substances reported willingness to use DPS to measure PrEP adherence in a research context, and identified benefits to accessing real-time, DPS-detected adherence data.
    Type of Medium: Online Resource
    ISSN: 2044-6055 , 2044-6055
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.1136/bmjopen-2022-067549
    DOI: 10.1136/bmjopen-2022-067549.supp1
    DOI: 10.1136/bmjopen-2022-067549.supp2
    Language: English
    Publisher: BMJ
    Publication Date: 2023
    detail.hit.zdb_id: 2599832-8
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  • 8
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    Structural Life Instability and Factors Related to Latino Sexual Minority Men’s Intention to Engage with Biomedical HIV-Prevention Services
    Springer Science and Business Media LLC ; 2022
    In:  AIDS and Behavior Vol. 26, No. 12 ( 2022-12), p. 3914-3924
    Details
    In: AIDS and Behavior, Springer Science and Business Media LLC, Vol. 26, No. 12 ( 2022-12), p. 3914-3924
    Type of Medium: Online Resource
    ISSN: 1090-7165 , 1573-3254
    URL: Article
    DOI: 10.1007/s10461-022-03718-1
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2014832-X
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  • 9
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    Sexual Minority Stress and Cellular Aging in Methamphetamine-Using Sexual Minority Men With Treated HIV
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Psychosomatic Medicine Vol. 84, No. 8 ( 2022-10), p. 949-956
    Details
    In: Psychosomatic Medicine, Ovid Technologies (Wolters Kluwer Health), Vol. 84, No. 8 ( 2022-10), p. 949-956
    Abstract: Sexual minority men (e.g., gay, bisexual, and other men who have sex with men) experience stigma and sexual minority stress, which are theorized to drive negative health outcomes. Sexual minority men with treated HIV display persistent immune dysregulation, which could be amplified by sexual minority stress responses to potentiate cellular aging. Methods This cross-sectional study included 52 sexual minority men living with HIV who had undetectable viral load ( 〈 40 copies/mL) and biologically confirmed recent methamphetamine use. Participants completed measures assessing sexual minority stress and openness about sexual minority status (i.e., outness). DNA methylation–derived outcomes included the following: the extrinsic epigenetic age acceleration clock, telomere length, naive CD4+ T-helper cells, and naive CD8+ T-cytotoxic/suppressor cells. Results After adjusting for negative affect and recent stimulant use, higher sexual minority stress was associated with a faster extrinsic epigenetic age acceleration clock ( β = 0.29, p = .030), shorter telomere length ( β = −0.43, p = .002), and fewer naive CD4+ (β = −0.57, p 〈 .001) and naive CD8+ T cells ( β = −0.57, p 〈 .001). Greater outness was associated with higher naive CD4+ ( β = 0.32, p = .030) and naive CD8+ T cells ( β = 0.38, p = .008) as well as lower plasma interleukin 6 ( β = −0.33, p = .027). Conclusions Sexual minority stress processes are associated with markers of cellular aging and inflammation in methamphetamine-using sexual minority men living with HIV. Longitudinal research should elucidate biobehavioral mechanisms linking sexual minority stress processes with accelerated cellular aging in those with and without HIV.
    Type of Medium: Online Resource
    ISSN: 1534-7796 , 0033-3174
    URL: Article
    DOI: 10.1097/PSY.0000000000001123
    RVK:
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    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
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  • 10
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    High Levels of Syndemics and Their Association with Adherence, Viral Non-suppression, and Biobehavioral Transmission Risk in Miami, a U.S. City with an HIV/AIDS Epidemic
    Springer Science and Business Media LLC ; 2019
    In:  AIDS and Behavior Vol. 23, No. 11 ( 2019-11), p. 2956-2965
    Details
    In: AIDS and Behavior, Springer Science and Business Media LLC, Vol. 23, No. 11 ( 2019-11), p. 2956-2965
    Type of Medium: Online Resource
    ISSN: 1090-7165 , 1573-3254
    URL: Article
    DOI: 10.1007/s10461-019-02619-0
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2019
    detail.hit.zdb_id: 2014832-X
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