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People with HIV (PWH) smoke at higher rates compared with the general population and have lower cessation rates. The primary aim of this study was to examine the impact of the COVID-19 pandemic on smoking in PWH. A survey was administered to participants in two smoking cessation trials in the United States. Mean cigarettes per day was 13.9 (SD 8.6), and participants reported they had smoked on average for 30.93 years (SD 10.4). More than half (55.7%) of participants (N = 140) reported not changing their smoking during the pandemic, while 15% reported decreasing, and 25% reported increasing their smoking. In bivariate analyses, worrying about food due to lack of money (χ

Although extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE) and carbapenem-resistant Enterobacterales (CRE) are a global challenge, data on these organisms in low- and middle-income countries are limited. In this study, we sought to characterize colonization data critical for greater antibiotic resistance surveillance efforts.This study was conducted in three hospitals and six clinics in Botswana. We conducted ongoing surveillance of adult patients in hospitals and clinics and adults and children in the community. All participants underwent rectal swab sampling to identify ESCrE and CRE.Enrollment occurred from January 15, 2020, to September 4, 2020, but paused from April 2, 2020, to May 21, 2020, because of a countrywide COVID-19 lockdown. Of 5088 individuals approached, 2469 (49%) participated. ESCrE colonization prevalence was 30.7% overall (43% for hospital participants, 31% for clinic participants, 24% for adult community participants, and 26% for child community participants) (P0.001). A total of 42 (1.7%) participants were colonized with CRE. CRE colonization prevalence was 1.7% overall (6.8% for hospital participants, 0.7% for clinic participants, 0.2% for adult community participants, and 0.5% for child community participants) (P0.001). ESCrE and CRE prevalence varied substantially across regions and was significantly higher prelockdown versus postlockdown.ESCrE colonization was high in all settings in Botswana. CRE prevalence in hospitals was also considerable. Colonization prevalence varied by region and clinical setting and decreased after a countrywide lockdown.

Postmodern music therapy is an approach to music therapy that defines itself in diametric opposition to modernist, or medical-model, music therapy. Where modernist music therapy ignores power dynamics and assumes itself to be value neutral, postmodern music therapy is concerned with power dynamics between client, therapist, and broader society. Postmodern music therapy is based on the theories of Bradley Lewis: Lewis (2006) believes that a postmodern psychiatry (or as he calls it, postpsychiatry) will be more aware of politics and social structures in general and will move toward democratization. This article proposes a postmodern music therapy in parallel to postpsychiatric ideas and ideals. Further, the article explores the intersectional nexus between postmodern music therapy and critical race, disability, queer, and feminist studies.

Background Clinical decision support (CDS) is a promising intervention for improving uptake of HIV testing and pre-exposure prophylaxis (PrEP). However, little is known regarding provider perspectives on acceptability, appropriateness, and feasibility of CDS for HIV prevention in pediatric primary care, a key implementation setting. Methods This was a cross-sectional multiple methods study utilizing surveys and in-depth interviews with pediatricians to assess acceptability, appropriateness, and feasibility of CDS for HIV prevention, as well as to identify contextual barriers and facilitators to CDS. Qualitative analysis utilized work domain analysis and a deductive coding approach grounded in the Consolidated Framework of Implementation Research. Quantitative and qualitative data were merged to develop an Implementation Research Logic Model to conceptualize implementation determinants, strategies, mechanisms, and outcomes of potential CDS use. Results Participants (n = 26) were primarily white (92%), female (88%), and physicians (73%). Using CDS to improve HIV testing and PrEP delivery was perceived as highly acceptable (median score 5), IQR [4–5]), appropriate (5, IQR [4–5]), and feasible (4, IQR [3.75–4.75]) using a 5-point Likert scale. Providers identified confidentiality and time constraints as two key barriers to HIV prevention care spanning every workflow step. With respect to desired CDS features, providers sought interventions that were integrated into the primary care workflow, standardized to promote universal testing yet adaptable to the level of a patient’s HIV risk, and addressed providers’ knowledge gaps and bolstered self-efficacy in providing HIV prevention services. Conclusions This multiple methods study indicates that clinical decision support in the pediatric primary care setting may be an acceptable, feasible, and appropriate intervention for improving the reach and equitable delivery of HIV screening and PrEP services. Design considerations for CDS in this setting should include deploying CDS interventions early in the visit workflow and prioritizing standardized but flexible designs.

In this paper we present findings from a systematic review on job creation, quality, and skills, focusing on decarbonisation in the energy sector. We compare a range of gross job employment factors which indicate that overall, investment in renewable energy and energy efficiency can deliver more jobs than gas or coal power generation. In addition, we review a subset of recent studies which estimate the net employment effects of decarbonisation in the energy sector at a national scale, across various international contexts. These national studies largely agree that the most likely outcome over the next few decades is a modest net positive creation of jobs and moderate economic growth. In certain regions within these countries, jobs in fossil fuel industries may be lost faster than the pace at which low carbon energy sectors can offer new employment. There may be mismatches between regions where displaced workers live and where new opportunities become available, which may be a barrier to accepting alternative employment even if former workers have the requisite skills. In these cases national government transition plans are recommended, co-ordinated with local governments, to manage the impacts of displacement from carbon intensive sectors and respond to the need to build a new low carbon workforce including through skills development and training. We highlight a lack of metrics and data in the literature on job quality, skills, and the geographic distribution of employment impacts in decarbonising energy systems, and these should be priority areas for further research.

ImportanceHIV self-testing (HIVST) is a promising strategy to expand the HIV care continuum, particularly among priority populations at high risk of HIV infection. However, little is known about HIVST uptake among men who have sex with men (MSM) outside of clinical trial settings.ObjectiveTo evaluate HIVST use among urban MSM in the US who reported testing within the past 12 months.Design, Setting, and ParticipantsA cross-sectional study of adult MSM in the 2017 National HIV Behavioral Surveillance system, which used venue-based sampling methods to collect data related to HIV testing, receipt of prevention services, and risk factors for HIV, was conducted at 588 venues in 23 urban areas in the contiguous US and Puerto Rico. All participants were offered HIV testing. Adult cisgender MSM who reported HIV-negative or unknown HIV status and obtained HIV testing in the past 12 months were included. Data for this study were collected between June 4, 2017, and December 22, 2017, and analyzed between October 23, 2020, and August 20, 2021.Main Outcomes and MeasuresSelf-reported HIVST in the past year. Adjusted prevalence ratios (aPRs) using survey weights were calculated to assess factors associated with HIVST.ResultsA total of 6563 MSM in 23 urban areas met inclusion criteria, of whom 506 (7.7%) individuals reported HIVST in the past year. The median age of self-testers was 29 (IQR, 25-35) years, 52.8% had completed college, and 37.9% reported non-Hispanic White race. One self-tester reported seroconverting in the prior 12 months, and an additional 10 self-testers were diagnosed with HIV during the survey. HIVST was associated with sexual orientation disclosure (aPR, 10.27; 95% CI, 3.45-30.60; P P = .01), younger age (aPR, 0.74; 95% CI, 0.66-0.84; P P = .01), and higher income levels (aPR, 1.18; 95% CI, 1.04-1.32; P = .009). No association was noted with condomless anal sex (aPR, 0.96; 95% CI, 0.88-1.06, P = .88), sexually transmitted infections (aPR, 0.96; 95% CI, 0.70-1.30; P = .77), or preexposure prophylaxis use (aPR, 0.99; 95% CI, 0.75-1.30; P = .92).Conclusions and RelevanceIn this study, HIVST was relatively uncommon in this sample of urban MSM. HIVST may not be reaching those with lower socioeconomic status or who have not disclosed their sexual identity. The findings of this study suggest that efforts to increase HIVST should focus on engaging underserved and vulnerable subgroups of MSM.

Background The epidemiology of ESCrE in low- and middle-income countries (LMICs) is poorly described. While risk factors for ESCrE clinical infection have been studied, little is known of the epidemiology of ESCrE colonization. Identifying risk factors for ESCrE colonization specifically is nonetheless critical to inform antibiotic resistance reduction strategies. Methods This study was conducted in 6 clinics located in 3 districts in Botswana. In each clinic, we surveyed a random sample of outpatients. We also invited each enrolled clinic subject to refer up to 3 adults. Each adult clinic or community subject was also invited to refer their children. All subjects had rectal swabs collected which were inoculated onto chromogenic media for preliminary identification of ESCrE. Final identification and susceptibility testing were performed using MALDI-TOF MS and VITEK-2, respectively. Data were collected on demographics, comorbidities, antibiotic use, healthcare exposures, travel, and farm and animal contact. Subjects with ESCrE colonization (cases) were compared to non-colonized subjects (controls). Bivariable and multivariable analyses were conducted to identify risk factors for ESCrE colonization. Results Enrollment occurred from 1/15/20–9/4/20 and 2,000 subjects were enrolled. There were 959 (48.0%) clinic subjects, 477 (23.9%) adult community subjects, and 564 (28.2%) child community subjects. 725 (36.3%) subjects lived in the same household as another subject. The median (IQR) age was 30 (12–41) and 1,463 (73%) were female. There were 555 cases and 1,445 controls (i.e., 27.8% of subjects were ESCrE colonized). Unadjusted comparisons are noted in Table 1. Independent risk factors for ESCrE were younger age, hospital exposure, travel, and presence of an ESCrE colonized household member (Table 2). Conclusion ESCrE colonization was common and associated with several exposures. Our results suggest even modest healthcare exposure may be important in driving ESCrE. The strong link to household member ESCrE colonization highlights the potential role of household transmission or common exposure. These findings warrant further prospective studies and provide vital information to inform strategies to curb further emergence of ESCrE in LMICs. Disclosures All Authors: No reported disclosures.

Background: Clinical decision support (CDS) is a promising implementation strategy for improving uptake of HIV testing and pre-exposure prophylaxis (PrEP). However, little is known regarding provider perspectives on acceptability, appropriateness, and feasibility of CDS for HIV prevention in pediatric primary care, a key implementation setting. Methods: Cross-sectional mixed methods study utilizing surveys and in-depth interviews with pediatricians to 1) assess acceptability, appropriateness, and feasibility of CDS for HIV prevention, 2) assess optimal timing and contextual barriers and facilitators to CDS implementation, and 3) develop an Implementation Research Logic Model to conceptualize implementation determinants, mechanisms, and outcomes of potential CDS use. Interview scripts were grounded in the Consolidated Framework of Implementation Research. Qualitative analysis utilized a mixed inductive and deductive approach, and quantitative and qualitative data were merged to develop the logic model. Results: Participants (n=26) were primarily white (92%), female (88%), and physicians (73%). Using CDS to improve HIV testing and PrEP delivery was perceived as highly acceptable (median score 5), IQR [4-5]), appropriate (5, IQR [4-5]), and feasible (4, IQR [3.75-4.75]) using a five-point Likert scale. Providers identified confidentiality and time constraints as two key barriers to HIV prevention care spanning every workflow step. With respect to desired CDS features, providers sought interventions that were integrated into the primary care workflow; standardized to promote universal testing yet adaptable to the level of patient’s HIV risk; and addressed providers knowledge gaps and bolstered self-efficacy in providing HIV prevention services. Conclusions: This mixed methods study indicates that clinical decision support in the pediatric primary care setting may be an acceptable, feasible, and appropriate strategy for improving the reach and equitable delivery of HIV screening and PrEP. Design considerations for CDS in this setting should include deploying interventions early in the visit workflow, and prioritizing standardized but flexible designs.

PURPOSE Oral cancer is the sixth most common cancer worldwide and is the seventh most common in Botswana. Lack of improvement in oral cancer survival despite the availability of multiple treatment options may be due to the high prevalence of advanced stage at presentation. We identified risk factors for presenting with oral cancer at an advanced stage to facilitate interventions to reduce mortality from oral cancers. METHODS A retrospective cohort analysis was conducted among individuals with biopsy-confirmed oral cancer at Princess Marina Hospital in Gaborone, Botswana, between 2010 and 2020. Data collected included age at diagnosis, sex, place of residence, HIV status, oral cancer stage, and oral subsite. Multivariable analyses were controlled for age, sex, district of residence, and oral subsite. RESULTS Of the 218 records analyzed, 79% were male, 58% were HIV-positive, the median age was 56 years (interquartile range: 47-63), and 67% presented with advanced-stage disease. Cancers from hidden oral sites were more likely to present at an advanced stage with an adjusted odds ratio (OR) of 2.98 (95% CI, 1.29 to 6.89; P = .01). Residence in socioeconomically disadvantaged districts was associated with higher likelihood (OR, 2.36; 95% CI, 1.28 to 4.39; P = .01) of advanced stage presentation compared with other districts. HIV infection was not associated with risk of advanced lesion presentation (OR, 1; 95% CI, 0.61 to 1.61; P = .97). CONCLUSION Hidden oral cancer sites and residence in districts with limited access to care were risk factors for advanced oral cancer at the time of diagnosis in Botswana. These findings support a need to increase efforts to improve access to care and increase oral cancer awareness to decrease the burden of advanced oral cancer.

BackgroundImplementation mapping is a systematic, collaborative, and contextually-attentive method for developing implementation strategies. As an exemplar, we applied this method to strategy development for Managed Problem Solving Plus (MAPS+), an adapted evidence-based intervention for HIV medication adherence and care retention that will be delivered by community health workers and tested in an upcoming trial.MethodsIn Step 1: Conduct Needs Assessment, we interviewed 31 stakeholders to identify determinants of MAPS+ implementation in 13 clinics serving people with HIV in Philadelphia County. In Step 2: Develop Logic Model, we used these determinants as inputs for a working logic model guided by the Consolidated Framework for Implementation Research. In Step 3: Operationalize Implementation Strategies, our team held a virtual stakeholder meeting to confirm determinants. We synthesized stakeholder feedback, then identified implementation strategies that conceptually matched to determinants using the Expert Recommendations for Implementing Change taxonomy. Next, we operationalized implementation strategies with specific examples for clinic settings. We linked strategies to behavior change theories to allow for a mechanistic understanding. We then held a second virtual stakeholder meeting to present the implementation menu for feedback and glean generalizable insights for how these strategies could be operationalized in each stakeholder's clinic. In Step 4: Protocolize Strategies, we incorporated stakeholder feedback and finalized the implementation strategy menu.FindingsImplementation mapping produced a menu of 39 strategies including revise professional roles, identify and prepare champions, use warm handoffs, and change record systems. The process of implementation mapping generated key challenges for implementation strategy development: lack of implementation strategies targeting the outer setting (i.e., sociopolitical context); tension between a one-size-fits-all and individualized approach for all clinics; conceptual confusion between facilitators and strategies; and challenges in translating the implementation science lexicon for partners.ImplicationsThis case exemplar advances both MAPS+ implementation and implementation science methods by furthering our understanding of the use of implementation mapping to develop strategies that enhance uptake of evidence-based interventions. The implementation menu will inform MAPS+ deployment across Philadelphia in an upcoming hybrid trial. We will carry out Step 5: Test Strategies to test the effectiveness and implementation of MAPS+.

Statin discontinuation can have major negative health consequences. Studying the reasons for discontinuation can be challenging as traditional data collection methods have limitations. We propose an alternative approach using social media.We used natural language processing and machine learning to extract mentions of discontinuation of statin therapy from an online health forum, WebMD ( http://www.webmd.com ). We then extracted data according to themes and identified key attributes of the people posting for themselves.We identified 2121 statin reviews that contained information on discontinuing at least one named statin. Sixty percent of people posting declared themselves as female and the most common age category was 55-64 years. Over half the people taking statins did so for 6 months. By far the most common reason given (90%) was patient experience of adverse events, the most common of which were musculoskeletal and connective tissue disorders. The rank order of adverse events reported in WebMD was largely consistent with those reported to regulatory agencies in the US and UK. Data were available on age, sex, duration of statin use, and, in some instances, adverse event resolution and rechallenge. In some instances, details were presented on resolution of the adverse event and rechallenge.Social media may provide data on the reasons for switching or discontinuation of a medication, as well as unique patient perspectives that may influence continuation of a medication. This information source may provide unique data for novel interventions to reduce medication discontinuation.

Smoking contributes to significant morbidity and mortality in people with HIV. People with HIV have relatively high nicotine metabolism rates, as measured by the nicotine metabolite ratio (NMR, 3-hydroxycotinine/cotinine). A higher NMR is associated with difficulty quitting smoking. We hypothesized that HIV infection might upregulate nicotine metabolism.A retrospective study of male current smokers in the Multicenter AIDS Cohort Study who HIV seroconverted between 1985 and 1993.Eligibility included having plasma stored before and after confirmed HIV seroconversion and current tobacco use. Samples were selected from the closest available visits before (median 3.3 months) and after (median 9.4 months) seroconversion. Antiretroviral therapy use was exclusionary. Cotinine and 3-hydroxycotinine were measured using liquid chromatography-tandem mass spectrometry. We compared NMR from plasma pre-HIV and post-HIV infection using signed-rank tests. We targeted a sample size of 71 pairs to achieve 80% power to detect a 0.1 unit increase in NMR with P = 0.05.We analyzed paired samples from 78 participants; the median age was 34.5 years [interquartile range (IQR 29-40 years)]. The median NMR pre-HIV and post-HIV was 0.45 (IQR 0.32-0.54) and 0.46 (IQR 0.34-0.56), respectively. The median change in NMR postseroconversion was +0.01 (IQR -0.05, +0.09), P = 0.25. Stratification of median change in NMR by timing between samples or time since HIV seroconversion did not alter this finding.Acquiring HIV had no measurable effect on NMR. We postulate that upregulation of the NMR may be due to direct pharmacologic effects of HIV medications or metabolic changes in response to HIV infection.

ACTG A5288 was a strategy trial conducted in diverse populations from multiple continents of people living with HIV (PLWH) failing second-line protease inhibitor (PI)-based antiretroviral therapy (ART) from 10 low- and middle-income countries (LMICs). Participants resistant to lopinavir (LPV) and/or multiple nucleotide reverse transcriptase inhibitors started on third-line regimens that included raltegravir (RAL), darunavir/ritonavir (DRV/r) and/or etravirine (ETR) according to their resistance profiles. At 48 weeks, 87% of these participants achieved HIV-1 RNA ≤200 copies/ml. We report here long-term outcomes over 144 weeks.Study participants were enrolled from 2013 to 2015, prior to the availability of dolutegravir in LMICs. "Extended Follow-up" of the study started after the last participant enrolled had reached 48 weeks and included participants still on antiretroviral (ARV) regimens containing RAL, DRV/r and/or ETR at that time. RAL, DRV/r and ETR were provided for an additional 96 weeks (giving total follow-up of ≥144 weeks), with HIV-1 RNA measured at 48 and 96 weeks and CD4 count at 96 weeks after entry into Extended Follow-up. Proportion of participants with HIV-1 RNA ≤200 copies/ml was estimated every 24 weeks, using imputation if necessary to handle the different measurement schedule in Extended Follow-up; mean CD4 count changes were estimated using loess regression.Of 257 participants (38% females), at study entry, median CD4 count was 179 cells/mmThird-line regimens comprising of RAL, DRV/r and/or ETR were very well tolerated and had high rates of durable virologic suppression among PLWH in LMICs who were failing on second-line PI-based ART prior to the availability of dolutegravir.

PURPOSE Patients who are HIV-positive and have breast cancer have worse overall survival (OS) compared with patients who are HIV-negative. Pathologic complete response (pCR) and relative dose intensity (RDI) of chemotherapy are associated with survival. We assessed whether pCR and RDI rates were lower for patients who are HIV-positive and received neoadjuvant chemotherapy (NACT). METHODS This was a prospective cohort analysis of patients initiating NACT in Botswana (February 2017 to September 2019). Primary outcomes were pCR and RDI; secondary outcomes were OS and toxicity. HIV status and zidovudine (ZDV) treatment were stratification factors. Multivariable analysis was used to control for confounding. RESULTS In total, 26 of 110 enrolled individuals were HIV-positive. In univariable analysis, HIV-positive (odds ratio [OR] = 0.2; P = .048) and RDI < 0.85 (OR = 0.30; P = .025) were associated with pCR. In multivariable analysis, the magnitude of association decreased for HIV-positive (OR = 0.28; P = .11), but RDI < 0.85 remained independently associated with pCR (OR = 0.32; P = .035). Patients who are HIV-positive had significantly lower mean RDI, and those on ZDV had significantly lower RDI. Ninety-one (83%) were stage III with 2-year OS significantly worse for patients who are HIV-positive (58% v 74%). Hazard ratio for all-cause mortality was 2.68 (95% CI, 1.17 to 6.13; P = .028) in patients who are HIV-positive compared with patients who are HIV-negative. Toxicity rates were similar despite patients who are HIV-positive receiving significantly lower dose intensity chemotherapy. CONCLUSION Patients who are HIV-positive and have breast cancer in Botswana have lower pCR rates and also receive lower dose intensity therapy, which may contribute to worse OS. Patients who are HIV-positive on ZDV-containing regimens received even lower dose intensity of NACT. Administering optimal dose intensity in patients who are HIV-positive remains a challenge, and targeted interventions that address modifiable risk factors are needed to improve therapy delivery and outcomes.

The impact of variable renewable energy (VRE) sources on an electricity system depends on technological characteristics, demand, regulatory practices and renewable resources. The costs of integrating wind or solar power into electricity networks have been debated for decades yet remain controversial and often misunderstood. Here we undertake a systematic review of the international evidence on the cost and impact of integrating wind and solar to provide policymakers with evidence to inform strategic choices about which technologies to support. We find a wide range of costs across the literature that depend largely on the price and availability of flexible system operation. Costs are small at low penetrations of VRE and can even be negative. Data are scarce at high penetrations, but show that the range widens. Nonetheless, VRE sources can be a key part of a least-cost route to decarbonization. As the cost of variable renewable energy generation has fallen and its proportion in power mixes has increased, discussion of its integration costs has intensified. Heptonstall and Gross systematically review the literature on these costs and asses the range of impacts it is shown to have.

Treatment management after repeated failure of antiretroviral therapy (ART) is difficult due to resistance and adherence challenges. For people who have failed non-nucleoside reverse transcriptase inhibitor-(NNRTI-) and protease inhibitor-(PI-) based regimens with no or limited resistance, remaining on PI-based ART is an option. Using data from an ART strategy trial (A5288) in low/middle-income countries which included this option, we explored whether predictors can be identified distinguishing those who experienced further virologic failure from those who achieved and maintained virologic suppression.A5288 enrolled people with confirmed HIV-1 RNA ≥ 1000 copies/mL after ≥ 24 weeks of PI-based ART and prior failure on NNRTI-based ART. This analysis focused on the 278 participants with no resistance to the PI being taken and no or limited nucleoside reverse transcriptase inhibitor (NRTI) resistance, who continued their PI with flexibility to change NRTIs. Proportional hazards models were used to evaluate predictors of virologic failure during follow-up (VF: confirmed HIV-1 RNA ≥ 1000 copies/mL at ≥ 24 weeks of follow-up).56% of participants were female. At study entry, median age was 40 years, time on ART 7.8 years, CD4 count 169 cells/mmA simple count of five predictors might have value for identifying risk of continued VF. Novel antiretroviral and adherence support interventions are needed to improve virologic outcomes for higher risk individuals.

We consider a semi-random walk on the space X of lattices in Euclidean n-space which attempts to maximize the sphere-packing density function Φ. A lattice (or its corresponding quadratic form) is called “sticky” if the set of directions in X emanating from it along which Φ is infinitesimally increasing has measure 0 in the set of all directions. Thus the random walk will tend to get “stuck” in the vicinity of a sticky lattice. We prove that a lattice is sticky if and only if the corresponding quadratic form is semi-eutactic. We prove our results in the more general setting of self-adjoint homogeneous cones. We also present results from our experiments with semi-random walks on X. These indicate some idea about the landscape of eutactic lattices in the space of all lattices.

Youth account for a disproportionate number of new HIV infections; however, pre-exposure prophylaxis (PrEP) use is limited. We evaluated PrEP counselling rates among non-Hispanic Black youth in the United States after a bacterial sexually transmitted infection (STI) diagnosis.We conducted a retrospective cohort study of Black youth receiving care at two academically affiliated clinics in Philadelphia between June 2014 and June 2019. We compared PrEP counselling for youth who received primary care services versus those who did not receive primary care services, all of whom met PrEP eligibility criteria due to STI diagnosis per U.S. Centers for Disease Control and Prevention clinical practice guidelines. Two logistic regression models for receipt of PrEP counselling were fit: Model 1 focused on sexual and gender minority (SGM) status and Model 2 on rectal STIs with both models adjusted for patient- and healthcare-level factors.Four hundred and sixteen patients met PrEP eligibility criteria due to STI based on sex assigned at birth and sexual partners. Thirty patients (7%) had documentation of PrEP counselling. Receipt of primary care services was not significantly associated with receipt of PrEP counselling in either Model 1 (adjusted OR (aOR) 0.10 [95% CI 0.01, 0.99]) or Model 2 (aOR 0.52 [95% CI 0.10, 2.77]). Receipt of PrEP counselling was significantly associated with later calendar years of STI diagnosis (aOR 6.80 [95% CI 1.64, 29.3]), assigned male sex at birth (aOR 26.2 [95% CI 3.46, 198]) and SGM identity (aOR 317 [95% CI 39.9, 2521]) in Model 1 and later calendar years of diagnosis (aOR 3.46 [95% CI 1.25, 9.58]), assigned male sex at birth (aOR 18.6 [95% CI 3.88, 89.3]) and rectal STI diagnosis (aOR 28.0 [95% CI 8.07, 97.5]) in Model 2. Fourteen patients (3%) started PrEP during the observation period; 12/14 (86%) were SGM primary care patients assigned male sex at birth.PrEP counselling and uptake among U.S. non-Hispanic Black youth remain disproportionately low despite recent STI diagnosis. These findings support the need for robust investment in PrEP-inclusive sexual health services that are widely implemented and culturally tailored to Black youth, particularly cisgender heterosexual females.

Harm reduction interventions, including SSP (Syringe Services Programs) and MAT (Medications for Addiction Treatment) have demonstrated the potential to help stem the epidemic of opioid use disorder. However, for that potential to be realized, people must expect that healthcare providers will be supportive if they ever seek care for substance use.This cross-sectional study investigated perceptions of provider support for SSP and MAT in the general population of 14 states selected specifically for 50 percent of the sample to include participants from rural counties with high rates of non-medical opioid use and injection. A survey of 3096 adults in 14 states and 675 counties within the Appalachian and Midwestern regions of the United States (collected between November of 2019 and May of 2020) examined the association between perceptions of provider support for harm reduction interventions, community members' trust of community healthcare providers, and expectations for patient-provider interactions involving disclosure of non-medical drug use.Path analysis supported the hypothesis that perceptions of provider support for harm reduction interventions predict positive expectations about patient-provider interactions and that trust in providers mediates this association. The model fit well among participants who reported past non-medical use of drugs and those who did not. In contrast to other research suggesting that trust in providers may be inconsequential during the initial stages of care, the current research suggests that trust may shape expectations about patient-provider interactions even before people use drugs. Communication of support for harm reduction interventions by providers may play an important role in promoting health care-seeking in populations that use drugs currently or who may use drugs in the future in high-risk rural areas of the United States.

PURPOSE Breast cancer patients, including patients living with HIV (PLWH), in sub-Saharan Africa experience a disproportionate burden of mortality. Adherence to treatment guidelines improves quality of care and survival outcomes. We therefore sought to study patient socioeconomic and cultural factors associated with treatment fidelity and how this may differ for PLWH in Botswana. METHODS This was a qualitative study design with deviance sampling of high and low fidelity patients who initiated treatment for stage I-III breast cancer. One-on-one phone interviews were conducted using semi-structured interviews, guided by the Theory of Planned Behavior. The final sample size was determined by thematic saturation. Transcribed interviews were double-coded and analyzed in NVivo using an integrated analysis approach. We maintained a kappa statistic of 0.8 between coders. RESULTS Fifteen high and 15 low fidelity patients were enrolled from August 25-December 15, 2020. Ten out of 30 of the cohort were PLWH. Barriers to treatment adherence included concerns about safety and efficacy of chemotherapy, lack of trust in the care team, lack of psychosocial support, financial toxicity, geographical inaccessibility, and other health-system barriers. Drivers and manifestations of stigma, including intersectional stigma of cancer fatalism in PLWH were identified as prominent barriers. Conversely, self-acceptance and de-stigmatization were identified as facilitators of treatment initiation. Additional facilitators included knowledge of curative intent, anticipated management of side effects, self-motivation, social support, and peer support. COVID-19 pandemic amplified existing socioeconomic barriers especially for patients with food insecurity and geographic inaccessibility. CONCLUSION The study identified multi-level modifiable patient and related health-system factors associated with treatment initiation and adherence. PLWH experienced unique barriers including intersectional stigma, which is a critical finding and warrants further evaluation. The facilitators in this study provide opportunities for leveraging existing strengths within the specific context to design multilevel implementation strategies to increase treatment fidelity of guideline concordant breast cancer therapy.

Arterial blood sampling (ABS) is considered the gold-standard method for evaluating the arterial input function in dynamic PET studies. However, ABS is invasive and associated with a high complexity and risks. Alternatively, image-derived input function (IDIF) methods can be employed to simplify protocols and enhance adoption of dynamic PET in research and clinical practice. However IDIF methods require scanning for longer periods at the scanner bed, can be limited by the short axial field-of-view (FOV) of the vast majority of modern clinical PET systems and are susceptible to noise and partial volume effects due to the large ring diameter and large detector elements size of modern clinical PET systems. In this work we are evaluating the physical performance of the SynchroPET ArterialPET™ scanner (Stony Brook, NY, USA), a human wrist standalone cylindrical PET prototype system of 9 cm diameter ring and 1.73 cm axial FOV, capable of 4D PET imaging of the human wrist to enhance existing IDIF methods. The NEMA NU4-2008 performance evaluation protocol was selected to assess spatial resolution. system sensitivity and image quality. All PET data were acquired in list-mode, later sorted into 3D sinograms and reconstructed with an open-source 3D-OSEM algorithm with all data corrections included (decay, randoms, normalization, attenuation and scatter) when applicable. The average of radial and transaxial resolution was 1.49mm and 2.78mm FWHM at 5mm and 25mm radial distance from the center, respectively, while the respective axial resolution was 2.84mm and 4.69mm FWHM. The system sensitivity was 3.54 kcps/MBq. In terms of image quality, all hot rod sources were distinguishable with recovery coefficients of 21.71% and 96.21% for the 1mm and 5mm rod sources, respectively. ArterialPET can be utilized to extract IDIF data from human arteries in the wrist where a 2-5mm diameter is expected. Further clinical studies are needed to assess potential enhancement of IDIF methods.

The rapid worldwide growth of renewable energy has been largely underpinned by government support over the past decade. The need for subsidy is fading as the cost of electricity from renewables converges with that from fossil fuels, but the withdrawal of support schemes will also remove the revenue stability offered by auction schemes and contracts for differences. Exposure to market risk (fluctuating wholesale electricity prices) raises the cost of capital for merchant renewable generators. Here we quantify the extent to which increased volatility in future power prices affects revenues by combining electricity market and stochastic discounted cash flow models. Renewable projects relying purely on merchant pricing may see cost of capital rise by two percentage points (e.g. from 7% to 9%). Unless new private or government actors provide hedging solutions, fewer developers will undertake new renewable energy projects, slowing the energy transition and increasing its cost to society.

Background Among the 1.2 million people living with HIV (PLWH) in the U.S., many are covered by Medicare, a federally funded health insurance program for elderly (≥65 years) and disabled (< 65 years) individuals. Medicare has emerged as a major source of HIV care for PLWH. Given limited research in this population, a better understanding of patient characteristics, comorbidities, and comedication use among PLWH in the Medicare program is needed to help optimize clinical care. Methods A retrospective claims analysis of a national cross-sectional sample of fee-for-service (FFS) Medicare beneficiaries with continuous medical and prescription coverage in 2018 was conducted using 100% Medicare administrative claims. The PLWH group included individuals with ≥1 HIV diagnosis code in medical claims and ≥1 pharmacy claim for an anchor antiretroviral (ARV) drug (i.e., NNRTI, PI or InSTI) in 2018. The comparison group included a random sample of Medicare beneficiaries without HIV (PLWoH). Sociodemographic characteristics, comorbidities, and medication use were compared between PLWH and PLWoH. Results The study sample included 86,856 PLWH and 552,645 PLWoH. PLWH were more likely to be younger (mean age: 57.4 vs 71.1 years and < 65 years: 72% vs 18%), male (75% vs 42%), Black (42% vs 10%), eligible for Medicare due to disability (83% vs 27%) and receiving full low-income subsidies (77% vs 31%); all p< 0.001. Prevalence of >3 comorbidities was high in PLWH (70.2%) and only slightly lower than in PLWoH (71.7% p< 0.001). Prevalence of neuropsychiatric conditions, chronic kidney disease, liver disease, COPD, hepatitis B, and hepatitis C were higher in PLWH (Figure 1). The mean hierarchical condition categories risk score was higher in PLWH vs PLWoH (1.81 vs. 1.32; p< 0.001). On average, polypharmacy was higher among PLWH vs PLWoH (annual number of unique medications: 12.6 vs. 9.4 for all drugs and 10.3 vs. 9.4 for non-ARV drugs, both p< 0.001). Figure 1. Percentage of PLWH and PLWoH with multimorbidity and selected comorbid conditions. Abbreviations: COPD=chronic obstructive pulmonary disease; GI=gastrointestinal; PLWH=people living with HIV; PLWoH=people living without HIV All p-values Conclusion In the Medicare FFS population, multimorbidity and polypharmacy were highly prevalent in PLWH despite their substantially younger age compared to PLWoH. Our findings highlight the need to consider comorbidities and comedications in HIV management including ARV regimens to minimize medication burden and drug interactions, which might improve clinical outcomes. Disclosures Pengxiang Li, PhD, Avalon Health Economics LLC (Consultant)COVIA Health Solutions (Consultant)Healthstatistics, LLC (Consultant) Jianbin Mao, PhD, Merck (Employee)Merck (Shareholder) Girish Prajapati, M.B.B.S., MPH , Merck & Co., Inc. (Employee, Shareholder) Robert Gross, MD, MSCE, Pfizer (Other Financial or Material Support, Serve on DSMB for drug unrelated to HIV) Jalpa A. Doshi, PhD, Acadia (Consultant, Advisor or Review Panel member)Allergan (Advisor or Review Panel member)Biogen (Grant/Research Support)Boehringer Ingelheim (Other Financial or Material Support, Scientific lecture)Catabasis (Consultant)Humana (Grant/Research Support)Janssen, Inc. (Consultant, Grant/Research Support)MeiraGTX (Consultant)Merck (Grant/Research Support, Advisor or Review Panel member)Novartis (Grant/Research Support)Otsuka (Advisor or Review Panel member)Regeneron (Grant/Research Support)SAGE Therapeutics (Consultant)Sanofi (Grant/Research Support)Shire (Advisor or Review Panel member)The Medicines Company (Advisor or Review Panel member)

Electrical energy storage has a critical role in future energy systems, but deployment is constrained by high costs and barriers to ‘stacking’ multiple revenue streams. We analyse the effects of different policy measures and revenue stacking on the economics of residential electricity storage in the UK. We identify six policy interventions through industry interviews and quantify their impact using a techno-economic model of a 4 kWh battery paired with a 4 kW solar system. Without policy intervention, residential batteries are not currently financially viable in the UK. Policies that enable access to multiple revenue streams, rather than just maximising PV self-consumption, improve this proposition. Demand Load-Shifting and Peak Shaving respectively increase the net present value per unit of investment cost (NPV/Capex) by 30 and 9 percentage points respectively. Given projected reductions in storage costs, stacking these services brings forward the break-even date for residential batteries by 9 years to 2024, and increases the effectiveness of policies that reduce upfront costs, suggesting that current policy is correctly focused on enabling revenue stacking. However, additional support is needed to accelerate deployment in the near term. Combining revenue stacking with a subsidy of £250 per kWh or zero-interest loans could make residential storage profitable by 2020.

Objective To determine whether regulatory variations in the heme oxygenase-1 (HO-1) promoter (GT)n dinucleotide repeat length could identify unique population genetic risks for neurocognitive impairment (NCI) in persons living with HIV (PLWH), we genotyped 528 neurocognitively assessed PLWH of European American and African American descent and linked genotypes to cognitive status. Methods In this cross-sectional study of PLWH (the CNS HIV Antiretroviral Therapy Effect Research cohort), we determined HO-1 (GT)n repeat lengths in 276 African Americans and 252 European Americans. Using validated criteria for HIV-associated NCI (HIV NCI), we found associations between allele length genotypes and HIV NCI and between genotypes and plasma markers of monocyte activation and inflammation. For comparison of HO-1 (GT)n allele frequencies with another population of African ancestry, we determined HO-1 (GT)n allele lengths in African PLWH from Botswana (n = 428). Results PLWH with short HO-1 (GT)n alleles had a lower risk for HIV NCI (OR = 0.63, 95% CI: 0.42–0.94). People of African ancestry had a lower prevalence of short alleles and higher prevalence of long alleles compared with European Americans, and in subgroup analyses, the protective effect of the short allele was observed in African Americans and not in European Americans. Conclusions Our study identified the short HO-1 (GT)n allele as partially protective against developing HIV NCI. It further suggests that this clinical protective effect is particularly relevant in persons of African ancestry, where the lower prevalence of short HO-1 (GT)n alleles may limit induction of HO-1 expression in response to inflammation and oxidative stress. Therapeutic strategies that enhance HO-1 expression may decrease HIV-associated neuroinflammation and limit HIV NCI.

AIDS Clinical Trial Group study A5202 (ClinicalTrials.gov identifier {"type":"clinical-trial","attrs":{"text":"NCT00118898","term_id":"NCT00118898"}}NCT00118898) was a phase 3b, randomized, partially blinded equivalence study of open-label atazanavir/ritonavir or efavirenz, plus either placebo-controlled tenofovir disoproxil fumarate/emtricitabine or abacavir/lamivudine, in treatment-naive adults living with HIV-1, evaluating efficacy, safety, and tolerability. We report an analysis of the contribution of participant characteristics to the disposition of tenofovir plasma concentrations. Tenofovir concentration data from a total of 817 individuals (88% of the total number of eligible patients randomly assigned to receive treatment in the TDF-containing arms of A5202) were available for analysis. Pharmacokinetic analysis was performed using nonlinear mixed-effects modeling. One- and two-compartment models with first-order absorption and first-order elimination were evaluated. An exponential error model was used for examination of interindividual variability (IIV), and a proportional and mixed-error model was assessed for residual variability. The final structural model contained two compartments with first-order absorption and elimination. IIV was estimated for apparent clearance (CL/F) and the first-order absorption rate constant (ka), and a proportional residual variability model was selected. The final mean parameter estimates were as follows: ka = 2.87 h−1, CL/F = 37.2 liters/h, apparent volumes of the central and peripheral compartments = 127 and 646 liters, respectively, and apparent intercompartmental clearance = 107 liters/h. In addition to race/ethnicity, creatinine clearance and assignment to atazanavir/ritonavir or efavirenz were significantly associated with CL/F (P < 0.001). In conclusion, race/ethnicity is associated with tenofovir oral CL in HIV-1 positive, treatment-naive adults. This covariate relationship raises questions about the possibility of differences in efficacy and risk of adverse events in different patient populations and suggests that examining preexposure prophylaxis regimens and tenofovir exposure in different race/ethnicity groups be considered.

In the United Kingdom, natural gas dominates the provision of heating in buildings. In Sweden, oil heating has been largely replaced by district heating and heat pumps. The origins and outcomes of path dependence and lock-in in heat-system evolution can be country specific. Here, we compare case studies of heat transitions in the United Kingdom and Sweden, addressing the question: can path dependency help to understand why these countries have followed different paths in terms of change to their heating infrastructure? In both countries, the development of heating infrastructures can be understood as path-dependent processes, entailing increasing returns to adoption as fuel sources, infrastructures and end-use technologies coevolve such that the overall performance of the system increases. The challenge for policymakers seeking to achieve carbon targets is to consider how to create the conditions to encourage increasing returns to adoption of low-carbon heating solutions. Domestic heating systems vary widely in their configurations across different countries. Here, Gross and Hanna use case studies of Sweden and the United Kingdom to explore the central roles of policies and path dependence in shaping the technologies and infrastructures providing domestic space heating.

Residential demands for space heating and hot water account for 31% of the total European energy demand. Space heating is highly dependent on ambient conditions and susceptible to climate change. We adopt a techno-economic standpoint and assess the impact of climate change on decentralised heating demand and the cost-optimal mix of heat pump and gas boiler technologies. Temperature data with high spatial resolution from nine climate models implementing three Representative Concentration Pathways from IPCC are used to estimate climate induced changes in the European demand side for heating. The demand side is modelled by the proxy of heating-degree days. The supply side is modelled by using a screening curve approach to the economics of heat generation. We find that space heating demand decreases by about 16%, 24% and 42% in low, intermediate and extreme global warming scenarios. When considering historic weather data, we find a heterogeneous mix of technologies are cost-optimal, depending on the heating load factor (number of full-load hours per year). Increasing ambient temperatures toward the end-century improve the economic performance of heat pumps in all concentration pathways. Cost optimal technologies broadly correspond to heat markets and policies in Europe, with some exceptions.

Fifteen years ago, Pacala and Socolow argued that global carbon emissions could be stabilised by mid-century using a portfolio of existing mitigation strategies. We assess historic progress for each of their proposed mitigation strategies and convert this into the unit of ‘wedges’. We show that the world is on track to achieve 1.5 ± 0.9 wedges relative to seven required to stabilise emissions, or 14 required to achieve net-zero emissions by mid-century. Substantial progress has been made in some domains that are not widely recognised (improving vehicle efficiency and declining vehicle use); yet this is tempered by negligible or even negative progress in many others (particularly tropical tree cover loss in Asia and Africa). By representing global decarbonisation efforts using the conceptually simple unit of wedges, this study helps a broader audience to understand progress to date and engage with the need for much greater effort over the coming decades.

Cost-effectively decarbonising the power sector and household energy use using variable renewable energy will require that electricity consumption becomes much more flexible and responsive to constraints in supply and the distribution network. In recent years residential demand response (DR) has received increasing attention that has sought to answer, based on current evidence, questions about how much consumers will engage with DR. This paper critically reviews the evidence base for residential consumer engagement with DR and draws out several important limitations in it. We argue for a more action-oriented focus on developing practical strategies to enable and unlock greater loadshifting and consumer engagement with DR within a changing technology and regulatory context. A number of recommendations are put forward for accelerating UK consumer engagement with DR, presented under three broad strategies: (a) promote awareness of smart tariffs, smart meters and storage and automation behind-the-meter devices as mutually-supportive components within a common ‘DR technology cluster’; (b) deliver targeted support for adoption of electric vehicles and other storage and automation technologies; (c) enable and support informed adoption of DR-enabling products and services through ‘smarter’ digital comparison tools (DCTs), data portability, and faster, simpler switching. The interdependency between components within this DR technology cluster delivers efficiency but also poses a risk that one delayed component (e.g., smart metering) will hold-up policy and industry support for other components. The urgency of decarbonisation goals makes it necessary to push forward as many of these elements as possible rather than the pace being set by the slowest.

Scenarios may be qualitative or quantitative, the latter of which can be developed using energy systems models. This study explores how different energy systems models and scenarios explicitly represent and assess potential disruptions and discontinuities. The focus is on futures studies and forward-looking scenario and modelling exercises. We apply definitions of ‘emergent’ (uncoordinated) and ‘purposive’ (coordinated) disruption to a systematic review on how energy systems models and scenarios have been used to capture disruption and discontinuity. We first conducted a review of reviews of energy models and scenarios to provide an overview of their common classifications. Additional searches then sought studies which use different types of models and scenarios to explore disruption and discontinuity. We analyse a subset of 30 of these modelling or scenario studies in which authors self-identify and represent disruption or discontinuity, finding that the most frequently used methods were qualitative, exploratory foresight scenarios or agent-based models. We conclude that policy makers could prepare more effectively for social, economic and political disruption by integrating multidisciplinary insights from social and political sciences, engineering and economics through a broader range of methods: exploratory, foresight scenarios, simulation and agent-based models and repurposed energy systems optimisation models.

Background: Neuromyelitis optica spectrum disorder (NMOSD) patients may be at increased risk of venous thromboembolism (VTE) not only due to ambulatory disability but also due to systemic autoimmune and inflammatory mechanisms altering the hemostatic balance. Objective: To compare the risk of VTE in NMOSD versus multiple sclerosis (MS) patients hospitalized for acute relapses. Methods: Hospital admissions for MS or NMOSD exacerbations were retrospectively identified. Demographics and medical history were recorded. The relationship between visit diagnosis and presence of VTE within 6 weeks of relapse onset was assessed by univariate logistic regression. A multivariate model evaluated the relationship between diagnosis, age, race, gender, body mass index (BMI), disease modifying therapy use, oral corticosteroid use, oral contraceptive use, smoking, length of stay (LOS), and ambulatory status on VTE risk. Results: A total of 30 NMOSD patients had 55 hospitalizations; 179 MS patients had 264 hospitalizations. Six NMOSD patients and one MS patient had VTE. NMOSD visits compared to MS visits had an odds ratio (OR) of VTE of 32.2 ( p = 0.002). NMOSD was more likely to be associated with VTE (OR = 17.4; p = 0.01) controlling for age, LOS, and ambulatory disability. Conclusion: NMOSD may be a risk factor for VTE. Larger prospective studies are required to confirm this risk and determine implications for prophylaxis.

OBJECTIVES/GOALS: Physician-scientists play a vital role in biomedical research but this chosen career path has many challenges, such as long training periods and funding. The University of Rochester (UR) CTSI pipeline programs address this by enabling medical trainees to partake in enriched research experiences. METHODS/STUDY POPULATION: The UR CTSI TL1 is a training grant from the National Center for Advancing Translational Science (NCATS), which funds predoctoral trainees. The TL1-funded physician-scientist pipeline includes the Academic Research Track (ART) year-out program and the Medical Science Training Program (MSTP). We describe the characteristics and training outcomes of TL1-funded trainees. We also obtained testimonials of current and former trainees regarding their career component decision-making, and their perception of programs, in order to identify how best to address the challenges of the physician-scientist workforce, and to facilitate the transition between the clinic and bench. RESULTS/ANTICIPATED RESULTS: From 2006-2019, the UR CTSI has had 56 ART trainees and 17 MSTP trainees complete training; six trainees have transitioned into the MSTP after completing the ART program. As of 2019, 63 of 67 graduated trainees (94%) have continued their engagement in CTS after graduation. Importantly, our programs have facilitated the careers of 31 women (39.7%) and 12 under-represented minorities (15.4%). We will present a breadth of qualitative data to inform which parts of the TL1-related programs have been successful, and which parts could use programmatic improvement to aid the transition into the physician-scientist workforce. DISCUSSION/SIGNIFICANCE OF IMPACT: Physician-scientist training barriers in the US have resulted in a shortage of these professionals in the clinical and translation workforce. Our data show the UR CTSI has been successful in addressing several of these challenges via the TL1-funded ART, MSTP, and ART/MSTP dual program pipeline.

Residential demand response (meaning changes to electricity use at specific times) has been proposed as an important part of the low carbon energy system transition. Modelling studies suggest benefits may include deferral of distribution network reinforcement, reduced curtailment of wind generation, and avoided investment in reserve generation. To accurately assess the contribution of demand response such studies must be supported by realistic assumptions on consumer participation. A systematic review of international evidence on trials, surveys and programmes of residential demand response suggests that it is important that these assumptions about demand response are not overly optimistic. Customer participation in trials and existing programmes is often 10% or less of the target population, while responses of consumers in existing schemes have varied considerably for a complex set of reasons. Relatively little evidence was identified for engagement with more dynamic forms of demand response, making its wider applicability uncertain. The evidence suggests that the high levels of demand response modelled in some future energy system scenarios may be more than a little optimistic. There is good evidence on the potential of some of the least ‘smart’ options, such as static peak pricing and load control, which are well established and proven. More research and greater empirical evidence is needed to establish the potential role of more innovative and dynamic forms of demand response.