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Preexposure prophylaxis (PrEP) for prevention of human immunodeficiency virus (HIV) infection may benefit not only the person who uses it but also their uninfected sexual risk contacts. We developed an agent-based model using a novel trial emulation approach to quantify disseminated effects of PrEP use among men who have sex with men in Atlanta, Georgia, from 2015 to 2017. Model components (subsets of agents connected through partnerships in a sexual network but not sharing partnerships with any other agents) were first randomized to an intervention coverage level or the control group; then, within intervention components, eligible agents were randomized to receive or not receive PrEP. We calculated direct and disseminated (indirect) effects using randomization-based estimators and report corresponding 95% simulation intervals across scenarios ranging from 10% coverage in the intervention components to 90% coverage. A population of 11,245 agents was simulated, with an average of 1,551 components identified. When comparing agents randomized to no PrEP in 70% coverage components with control agents, there was a 15% disseminated risk reduction in HIV incidence (risk ratio = 0.85, 95% simulation interval: 0.65, 1.05). Persons not on PrEP may receive a protective benefit by being in a sexual network with higher PrEP coverage. Agent-based models are useful for evaluating possible direct and disseminated effects of HIV prevention modalities in sexual networks.
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Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/prevención & control , Homosexualidad Masculina , Profilaxis Pre-Exposición , Adolescente , Adulto , Anciano , Georgia/epidemiología , Infecciones por VIH/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Modelos Estadísticos , Conducta SexualRESUMEN
Background: Disruptions in access to in-person human immunodeficiency virus (HIV) preventive care during the coronavirus disease 2019 (COVID-19) pandemic may have a negative impact on our progress towards the Ending the HIV Epidemic goals in the United States. Methods: We used an agent-based model to simulate HIV transmission among Black/African American men who have sex with men in Mississippi over 5 years to estimate how different reductions in access affected the number of undiagnosed HIV cases, new pre-exposure prophylaxis (PrEP) starts, and HIV incidence. Results: We found that each additional 25% decrease in HIV testing and PrEP initiation was associated with decrease of 20% in the number of cases diagnosed and 23% in the number of new PrEP starts, leading to a 15% increase in HIV incidence from 2020 to 2022. Conclusions: Unmet need for HIV testing and PrEP prescriptions during the COVID-19 pandemic may temporarily increase HIV incidence in the years immediately after the disruption period.
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BACKGROUND: We examined the impact of expanded access to medications for opioid use disorder (MOUD) in a unified prison and jail system on post-release, opioid-related overdose mortality. METHODS: We developed a microsimulation model to simulate a population of 55,000 persons at risk of opioid-related overdose mortality in Rhode Island. The effect of an extended-release (XR) naltrexone only intervention and the effect of providing access to all three MOUD (i.e., methadone, buprenorphine, and XR-naltrexone) at release from incarceration on cumulative overdose death over eight years (2017-2024) were compared to the standard of care (i.e., limited access to MOUD). RESULTS: In the standard of care scenario, the model predicted 2385 opioid-related overdose deaths between 2017 and 2024. An XR-naltrexone intervention averted 103 deaths (4.3% reduction), and access to all three MOUD averted 139 deaths (5.8% reduction). Among those with prior year incarceration, an XR-naltrexone only intervention and access to all three MOUD reduced overdose deaths by 22.8% and 31.6%, respectively. CONCLUSIONS: Expanded access to MOUD in prison and jail settings can reduce overdose mortality in a general, at-risk population. However, the real-world impact of this approach will vary by levels of incarceration, treatment enrollment, and post-release retention.
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Buprenorfina , Trastornos Relacionados con Opioides , Humanos , Cárceles Locales , Trastornos Relacionados con Opioides/tratamiento farmacológico , Prisiones , Rhode IslandRESUMEN
As HIV incidence among people who inject drugs grows in the context of an escalating drug overdose epidemic in North America, investigating how network structure may affect vulnerability to rapid HIV transmission is necessary for preventing outbreaks. We compared the characteristics of the observed contact tracing network from the 2015 outbreak in rural Indiana with 1000 networks generated by an agent-based network model with approximately the same number of individuals (n = 420) and ties between them (n = 913). We introduced an initial HIV infection into the simulated networks and compared the subsequent epidemic behavior (e.g., cumulative HIV infections over 5 years). The model was able to produce networks with largely comparable characteristics and total numbers of incident HIV infections. Although the model was unable to produce networks with comparable cohesiveness (where the observed network had a transitivity value 35.7 standard deviations from the mean of the simulated networks), the structural variability of the simulated networks allowed for investigation into their potential facilitation of HIV transmission. These findings emphasize the need for continued development of injection network simulation studies in tandem with empirical data collection to further investigate how network characteristics played a role in this and future outbreaks.
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Epidemias , Infecciones por VIH , Preparaciones Farmacéuticas , Abuso de Sustancias por Vía Intravenosa , Trazado de Contacto , Infecciones por VIH/epidemiología , Humanos , Abuso de Sustancias por Vía Intravenosa/epidemiologíaRESUMEN
OBJECTIVE: We aimed to determine the effectiveness of various preexposure prophylaxis (PrEP) prescription strategies for African-American women impacted by mass incarceration within an urban setting. DESIGN: An agent-based model was utilized to evaluate prevention strategies in an efficient, ethical manner. By defining agents, their characteristics and relationships, we assessed population-level effects of PrEP on HIV incidence. METHODS: We tested hypothetical PrEP prescription strategies within a simulation representing the African-American population of Philadelphia, Pennsylvania. Four strategies were evaluated: PrEP for women meeting CDC indicators regarding partner characteristics, PrEP for women with a recently incarcerated male partner, PrEP for women with a recently released male partner and couples-based PrEP at time of release. Interventions occurred alongside scale-up of HAART. We evaluated reductions in HIV transmissions, the number of persons on PrEP needed to avert one HIV transmission (NNT) and the resulting proportions of people on PrEP. RESULTS: Scenarios prescribing PrEP based on criminal justice system involvement reduced HIV transmissions. The NNT ranged from 147 (couples-based scenario) to 300 (recently released scenario). The percentage of the female population covered by PrEP at any one time ranged from 0.14% (couples-based) to 10.8% (CDC-based). CDC-guideline scenarios were consistently less efficient compared to the justice-involved interventions. CONCLUSION: Expanding PrEP for African-American women and their male partners affected by incarceration should be considered in national HIV prevention goals and correctional facilities leveraged as intervention sites. Partner characteristics in the current CDC indications may be more effective and efficient if guidelines considered criminal justice involvement.
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Fármacos Anti-VIH , Infecciones por VIH , Profilaxis Pre-Exposición , Negro o Afroamericano , Fármacos Anti-VIH/uso terapéutico , Terapia Antirretroviral Altamente Activa , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/prevención & control , Humanos , Incidencia , MasculinoRESUMEN
BACKGROUND: It is unknown what levels of preexposure prophylaxis (PrEP) use are needed to reduce racial disparities in HIV incidence among men who have sex with men (MSM). Using an agent-based model, we quantified the impact of achieving PrEP coverage targets grounded in equity on racial disparities in HIV incidence among MSM in an urban setting in the Southeastern United States. METHODS: An agent-based model was adapted to simulate HIV transmission in a network of Black/African American and White MSM aged 18-39 years in the Atlanta-Sandy Springs-Roswell metropolitan area over 10 years (2015-2024). Scenarios simulated coverage levels consistent with targets based on the ratio of the number of individuals using PrEP to the number of individuals newly diagnosed in a calendar year (i.e., the 'PrEP-to-need ratio'), ranging from 1 to 10. Incidence rate ratios and differences were calculated as measures of disparities. RESULTS: Without PrEP, the model predicted a rate ratio of 3.82 and a rate difference of 4.50 comparing HIV incidence in Black/African American and White MSM, respectively. Decreases in the rate ratio of at least 50% and in the rate difference of at least 75% were observed in all scenarios in which the PrEP-to-need ratio among Black/African American MSM was 10, regardless of the value among White MSM. CONCLUSION: Significant increases in PrEP use are needed among Black/African American MSM to reduce racial disparities in HIV incidence. PrEP expansion must be coupled with structural interventions to address vulnerability to HIV infection among Black/African American MSM.
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Infecciones por VIH , Equidad en Salud , Disparidades en Atención de Salud , Profilaxis Pre-Exposición , Grupos Raciales , Minorías Sexuales y de Género , Adolescente , Adulto , Negro o Afroamericano , Georgia , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Humanos , Incidencia , Masculino , Población Blanca , Adulto JovenRESUMEN
The mechanism of gold(i)-thiolate, disulfide exchange was investigated by using initial-rate kinetic studies, 2D ((1)H-(1)H) ROESY NMR spectroscopy, and electrochemical/chemical techniques. The rate law for exchange is overall second order, first order in gold(i)-thiolate and disulfide. 2D NMR experiments show evidence of association between gold(i)-thiolate and disulfide. Electrochemical/chemical investigations do not show evidence of free thiolate and are consistent with a mechanism involving formation of a [Au-S, S-S], four-centered metallacycle intermediate during gold(i)-thiolate, disulfide exchange.
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We measured plasma catecholamines, alpha- and beta-adrenoreceptor numbers and the accumulation of cyclic adenosine monophosphate (cAMP) in the unstimulated state and in response to 10 mumol/l (-) isoproterenol in blood cells from 29 euthyroid controls and from 18 patients with spontaneous hyperthyroidism. In the thyrotoxic patients plasma norepinephrine (1.14 +/- 0.5 nmol/l) and epinephrine (0.3 +/- 0.14 nmol/l) were significantly decreased compared with plasma norepinephrine (1.87 +/- 0.7 nmol) and epinephrine (0.41 +/- 0.19 nmol/l) in the controls (P less than 0.01 and P less than 0.05, respectively) and the values obtained in subjects rendered euthyroid by antithyroid treatment (P less than 0.001, respectively). alpha-adrenoceptor density in platelet membranes obtained from patients in the hyperthyroid state (114 +/- 38 sites per cell) was significantly decreased when compared with controls (159 +/- 48 sites per cell, P less than 0.01) and the values from patients under effective antithyroid treatment (136 +/- 35 sites per cell, P less than 0.01). On the contrary, a significant increase in beta-adrenoceptor density in mononuclear leucocyte (MNL) membranes was found in hyperthyroid patients (1751 +/- 237 sites/cell) when compared with controls (1510 +/- 351 sites/cell, P less than 0.05) and the same patients following antithyroid treatment (1455 +/- 260 sites/cell, P less than 0.001). The equilibrium dissociation constants (KD) did not change in hyperthyroidism. Basal cAMP concentrations in MNL were higher in untreated thyrotoxicosis (45 +/- 18 pmol/10(6) cells/10 min) than in patients in the euthyroid state (35 +/- 9 pmol/10(6) cells/10 min, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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Antitiroideos/uso terapéutico , Plaquetas/metabolismo , Epinefrina/sangre , Hipertiroidismo/sangre , Monocitos/metabolismo , Norepinefrina/sangre , Receptores Adrenérgicos alfa/metabolismo , Receptores Adrenérgicos beta/metabolismo , Adenilil Ciclasas/sangre , Adulto , Anciano , Membrana Celular/metabolismo , AMP Cíclico/sangre , Dihidroalprenolol/sangre , Femenino , Humanos , Hipertiroidismo/tratamiento farmacológico , Isoproterenol/farmacología , Masculino , Persona de Mediana Edad , Yohimbina/sangreRESUMEN
Through The Rehabilitation Act, the Technology Related Assistance for Individuals with Disabilities Act (The Tech Act), the Individuals with Disabilities Education Act (IDEA), and the Americans with Disabilities Act (ADA) of 1990, the federal government broadened the states' roles in increasing awareness and accessibility of assistive technology (AT) devices and services to children with disabilities. As a member of the AT team, the occupational therapy practitioner plays an integral role in selecting the most appropriate device, and working with parents and other professionals to integrate the device into a child's daily routines. This literature review presents a summary of available information on AT materials and strategies that assist infants, toddlers, and school-aged children with disabilities. We begin with a brief look at legislation affecting the provision of AT. Issues concerning the use of Electronic Aides of Daily Living (EADL), and strategies for successful manipulation are presented; followed by a discussion of play and leisure, mobility, and communication devices. Finally, we conclude with a discussion concerning the importance of measuring the effectiveness of AT devices and services.