Evaluation of the Impact and Outcomes of a Rapid Transition to Telehealth PrEP Delivery at a Sexual Health Clinic During the COVID-19 Pandemic.

BACKGROUND: Increasing human immunodeficiency virus (HIV) preexposure prophylaxis (PrEP) use is a critical part of ending the HIV epidemic. In response to the COVID-19 pandemic, many PrEP services transitioned to a telehealth model (telePrEP). This report evaluates the effect of COVID-19 and the addition of telePrEP on delivery of PrEP services at the Denver Sexual Health Clinic (DSHC), a regional sexual health clinic in Denver, CO. METHODS: Before COVID-19, DSHC PrEP services were offered exclusively in-clinic. In response to the pandemic, after March 15, 2020, most PrEP initiation and follow-up visits were converted to telePrEP. A retrospective analysis of DSHC PrEP visits compared pre-COVID-19 (September 1, 2019 to March 15, 2020) to post-COVID-19 (March 16, 2020 to September 30, 2020) visit volume, demographics, and outcomes. RESULTS: The DSHC completed 689 PrEP visits pre-COVID-19 and maintained 96.8% (n = 667) of this volume post-COVID-19. There were no differences in client demographics between pre-COVID-19 (n = 341) and post-COVID-19 PrEP start visits (n = 283) or between post-COVID-19 in-clinic (n = 140) vs telePrEP start visits (n = 143). There were no differences in 3- to 4-month retention rates pre-COVID-19 (n = 17/43) and post-COVID-19 (n = 21/43) ( P = 0.52) or between in-clinic (n = 12/21) and telePrEP clients (n = 9/22) in the post-COVID-19 window ( P = 0.37). Also, there were no significant differences in lab completion rates between in-clinic (n = 140/140) and telePrEP clients (n = 138/143) ( P = 0.06) and prescription fill rates between in-clinic (n = 115/136) and telePrEP clients (n = 116/135) in the post-COVID-19 window ( P = 0.86). CONCLUSIONS: Implementation of TelePrEP enabled the DSHC to sustain PrEP services during the COVID-19 pandemic without significant differences in demographics, engagement, or retention in PrEP services.

Berkeleylactones and a Citreohybriddione Analogue from Penicillium turbatum.

In 2017 we reported the isolation and characterization of berkeleylactones A-H and A26771B from a coculture of two extremophilic Penicillium sp. isolated from an acid mine waste lake. Berkeleylactone A exhibited potent activity against several strains of multi-drug-resistant Staphylococcus aureus and Bacillus anthracis. A26771B, which is related to the berkeleylactones, also exhibited antibiotic activity. Although the berkeleylactones were novel compounds, A26771B was originally isolated by scientists at Eli Lilly Company from P. turbatum and reported in1977. We recently obtained P. turbatum and grew it in axenic culture. We isolated five new berkeleylactones (2 and 4-7), two berkeley-γ-lactones (8 and 9), and citreohybriddional (10), as well as the known compounds A26771B (1), berkeleylactone E (3), and gliovictin. The structures of the novel compounds were deduced from analysis of spectral data. Compounds 2 and 4 -7 are 16-membered macrolides, while 8 and 9 are γ-lactones that share the hexadecanoic acid skeleton. A26771B (1) and berkeleylactone I (2) were active against several strains of Staphylococcus aureus, including four multi-drug-resistant strains. Berkeleylactone N (8) was active only against Streptococcus pyogenes.

Toward Broad Spectrum Dihydrofolate Reductase Inhibitors Targeting Trimethoprim Resistant Enzymes Identified in Clinical Isolates of Methicillin Resistant Staphylococcus aureus.

The spread of plasmid borne resistance enzymes in clinical Staphylococcus aureus isolates is rendering trimethoprim and iclaprim, both inhibitors of dihydrofolate reductase (DHFR), ineffective. Continued exploitation of these targets will require compounds that can broadly inhibit these resistance-conferring isoforms. Using a structure-based approach, we have developed a novel class of ionized nonclassical antifolates (INCAs) that capture the molecular interactions that have been exclusive to classical antifolates. These modifications allow for a greatly expanded spectrum of activity across these pathogenic DHFR isoforms, while maintaining the ability to penetrate the bacterial cell wall. Using biochemical, structural, and computational methods, we are able to optimize these inhibitors to the conserved active sites of the endogenous and trimethoprim resistant DHFR enzymes. Here, we report a series of INCA compounds that exhibit low nanomolar enzymatic activity and potent cellular activity with human selectivity against a panel of clinically relevant TMP resistant (TMPR) and methicillin resistant Staphylococcus aureus (MRSA) isolates.

Global health ethics: critical reflections on the contours of an emerging field, 1977-2015.

BACKGROUND: The field of bioethics has evolved over the past half-century, incorporating new domains of inquiry that signal developments in health research, clinical practice, public health in its broadest sense and more recently sensitivity to the interdependence of global health and the environment. These extensions of the reach of bioethics are a welcome response to the growth of global health as a field of vital interest and activity. METHODS: This paper provides a critical interpretive review of how the term "global health ethics" has been used and defined in the literature to date to identify ethical issues that arise and need to be addressed when deliberating on and working to improve the discourse on ethical issues in health globally. RESULTS: Selected publications were analyzed by year of publication and geographical distribution, journal and field, level of engagement, and ethical framework. Of the literature selected, 151 articles (88%) were written by authors in high-income countries (HIC), as defined by the World Bank country classifications, 8 articles (5%) were written by authors in low- or middle-income countries (LMIC), and 13 articles (7%) were collaborations between authors in HIC and LMIC. All of the articles selected except one from 1977 were published after 1998. Literature on global health ethics spiked considerably from the early 2000s, with the highest number in 2011. One hundred twenty-seven articles identified were published in academic journals, 1 document was an official training document, and 44 were chapters in published books. The dominant journals were the American Journal of Bioethics (n = 10), Developing World Bioethics (n = 9), and Bioethics (n = 7). We coded the articles by level of engagement within the ethical domain at different levels: (1) interpersonal, (2) institutional, (3) international, and (4) structural. The ethical frameworks at use corresponded to four functional categories: those examining practical or narrowly applied ethical questions; those concerned with normative ethics; those examining an issue through a single philosophical tradition; and those comparing and contrasting insights from multiple ethical frameworks. CONCLUSIONS: This critical interpretive review is intended to delineate the current contours and revitalize the conversation around the future charge of global health ethics scholarship.

The use of background EEG activity to determine stimulus timing as a means of improving rTMS efficacy in the treatment of depression: a controlled comparison with standard techniques.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) treatment of depression utilizes numerous predetermined patterns of stimulation. As an alternative to using invariant stimulus timing parameters, the interactive technique delivers individual stimuli based on the background electroencephalogram (EEG) activity. OBJECTIVE: This study examines the use of an EEG-dependent technique as a means to enhance the efficacy of rTMS in the treatment of depression. METHODS: Forty-four patients with treatment-refractory major depression were treated, in a randomized, doubleblind, 4-week trial, with two different rTMS stimulus timing techniques (left dorsolateral prefrontal cortex). Standard rTMS utilized 10-Hz stimuli, whereas interactive rTMS applied individual stimuli in response to a selected pattern of background EEG activity analyzed in real time. Hamilton Depression Rating Scale (HDRS) and the Beck's Depression Inventory-II (BDI) scores were recorded at baseline, 2 weeks and after the final treatment. RESULTS: The interactive group showed a trend toward greater efficacy than the standard group in both absolute (t=-1.68; P=.100) and percentage (t=-1.74; P=.090) change in scores on HDRS (and similarly BDI). The response rate (>50% reduction) for the interactive technique of 43% (9/21) was also different to that of the standard technique (22%; 5/23; odds ratio: 2.70). CONCLUSIONS: The use of EEG-based TMS stimuli has been shown to be feasible in an rTMS clinical trial in treatment-resistant depression. The EEG-based interactive technique was associated with an indication of a trend toward a greater clinical effect than the standard rTMS technique. The interactive technique thus has the potential to refine the rTMS methodology and to enhance efficacy in the treatment of depression.

Priming media stereotypes reduces support for social welfare policies: the mediating role of empathy.

Two experiments involving White participants tested the influence of media-based priming of Black stereotypes on support for government policy that assisted Black versus White persons-in-need. Experiment 1 showed that priming the "Black criminal" stereotype through exposure to photographs of Blacks looting after Hurricane Katrina reduced policy support for Black evacuees-in-need but did not influence support responses toward White evacuees-in-need. Experiment 2 showed that priming the "promiscuous Black female" stereotype through exposure to sexual rap music reduced policy support for a Black pregnant woman-in-need but did not influence support responses toward a White pregnant woman-in-need. Further tests of mediated moderation demonstrated that in both experiments, the interactive influence of priming Black stereotypes and race of persons-in-need on policy support was mediated by empathic responding.