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OBJECTIVE: To compare preferences, uptake, and cofactors for unassisted home-based oral self-testing (HB-HIVST) versus clinic-based rapid diagnostic blood tests (CB-RDT) for maternal HIV retesting. DESIGN: Prospective cohort. METHODS: Between November 2017 and June 2019, HIV-negative pregnant Kenyan women receiving antenatal care were enrolled and given a choice to retest with HB-HIVST or CB-RDT. Women were asked to retest between 36 weeks gestation and 1-week post-delivery if the last HIV test was <24 weeks gestation or at 6 weeks postpartum if ≥24 weeks gestation, and self-report on retesting at a 14-week postpartum. RESULTS: Overall, 994 women enrolled and 33% (n = 330) selected HB-HIVST. HB-HIVST was selected because it was private (n = 224, 68%), convenient (n = 211, 63%), and offered flexibility in the timing of retesting (n = 207, 63%), whereas CB-RDT was selected due to the trust of providers to administer the test (n = 510, 77%) and convenience of clinic testing (n = 423, 64%). Among 905 women who reported retesting at follow-up, 135 (15%) used HB-HIVST. Most (n = 595, 94%) who selected CB-RDT retested with this strategy, compared to 39% (n = 120) who selected HB-HIVST retesting with HB-HIVST. HB-HIVST retesting was more common among women with higher household income and those who may have been unable to test during pregnancy (both retested postpartum and delivered <37 weeks gestation) and less common among women who were depressed. Most women said they would retest in the future using the test selected at enrollment (99% [n = 133] HB-HIVST; 93% [n = 715] CB-RDT-RDT). CONCLUSIONS: While most women preferred CB-RDT for maternal retesting, HB-HIVST was acceptable and feasible and could be used to expand HIV retesting options.
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Infecções por HIV , Autoteste , Humanos , Feminino , Quênia , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Adulto , Gravidez , Estudos Prospectivos , Adulto Jovem , Cuidado Pré-Natal , Complicações Infecciosas na Gravidez/diagnóstico , Teste de HIV/métodos , Preferência do Paciente/estatística & dados numéricos , Programas de Rastreamento/métodosRESUMO
INTRODUCTION: Assisted partner services (APS), or exposure notification and HIV testing for sexual partners of persons diagnosed HIV positive (index clients), is recommended by the World Health Organization. Most APS literature focuses on outcomes among index clients and their partners. There is little data on the benefits of providing APS to partners of partners diagnosed with HIV. METHODS: We utilized data from a large-scale APS implementation project across 31 facilities in western Kenya from 2018 to 2022. Females testing HIV positive at facilities were offered APS; those who consented provided contact information for all male sexual partners in the last 3 years. Male partners were notified of their potential HIV exposure and offered HIV testing services (HTS). Males newly testing positive were also offered APS and asked to provide contact information for their female partners in the last 3 years. Female partners of male partners (FPPs) were provided exposure notification and HTS. All participants with HIV were followed up at 12 months post-enrolment to assess linkage-to antiretroviral treatment (ART) and viral suppression. We compared HIV positivity, demographics and linkage outcomes among female index clients and FPPs. RESULTS: Overall, 5708 FPPs were elicited from male partners, of whom 4951 received HTS through APS (87% coverage); 291 FPPs newly tested HIV positive (6% yield), an additional 1743 (35.2%) reported a prior HIV diagnosis, of whom 99% were on ART at baseline. At 12 months follow-up, most FPPs were taking ART (92%) with very few adverse events: <1% reported intimate partner violence or reported relationship dissolution. FPPs were more likely than female index clients to report HIV risk behaviours including no condom use at last sex (45% vs. 30%) and multiple partners (38% vs. 19%). CONCLUSIONS: Providing HIV testing via APS to FPP is a safe and effective strategy to identify newly diagnosed females and achieve high linkage and retention to ART and can be an efficient means of identifying HIV cases in the era of declining HIV incidence. The high proportion of FPPs reporting HIV risk behaviours suggests APS may help interrupt community HIV transmission via increased knowledge of HIV status and linkage to treatment.
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Busca de Comunicante , Infecções por HIV , Ciência da Implementação , Parceiros Sexuais , Humanos , Quênia/epidemiologia , Feminino , Masculino , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/prevenção & controle , Adulto , Adulto Jovem , Busca de Comunicante/métodos , Teste de HIV/métodos , Pessoa de Meia-Idade , AdolescenteRESUMO
INTRODUCTION: Assisted partner services (APS) is an effective strategy for increasing HIV testing, new diagnosis, and linkage to care among sexual partners of people living with HIV (PLWH). APS can be resource intensive as it requires community tracing to locate each partner named and offer them testing. There is limited evidence for the effectiveness of offering HIV self-testing (HIVST) as an option for partner testing within APS. METHODS: We conducted a cluster randomized controlled trial comparing provider-delivered HIV testing (Standard APS) versus offering partners the option of provider-delivered testing or HIVST (APS+HIVST) at 24 health facilities in Western Kenya. Facilities were randomized 1:1 and we conducted intent-to-treat analyses using Poisson generalized linear mixed models to estimate intervention impact on HIV testing, new HIV diagnoses, and linkage to care. All models accounted for clustering at the clinic level and new diagnoses and linkage models were adjusted for individual-level age, sex, and income a priori. RESULTS: From March to December 2021, 755 index clients received APS and named 5054 unique partners. Among these, 1408 partners reporting a prior HIV diagnosis were not eligible for HIV testing and were excluded from analyses. Of the remaining 3646 partners, 96.9% were successfully contacted for APS and tested for HIV: 2111 (97.9%) of 2157 in the APS+HIVST arm and 1422 (95.5%) of 1489 in the Standard APS arm. In the APS+HIVST arm, 84.6% (1785/2111) tested via HIVST and 15.4% (326/2111) received provider-delivered testing. Overall, 16.7% of the 3533 who tested were newly diagnosed with HIV (APS+HIVST = 357/2111 [16.9%]; Standard APS = 232/1422 [16.3%]). Of the 589 partners who were newly diagnosed, 90.7% were linked to care (APS+HIVST = 309/357 [86.6%]; Standard APS = 225/232 [97.0%]). There were no significant differences between the two arms in HIV testing (relative risk [RR]: 1.02, 95% CI: 0.96-1.10), new HIV diagnoses (adjusted RR [aRR]: 1.03, 95% CI: 0.76-1.39) or linkage to care (aRR: 0.88, 95% CI: 0.74-1.06). CONCLUSIONS: There were no differences between APS+HIVST and Standard APS, demonstrating that integrating HIVST into APS continues to be an effective strategy for identifying PLWH by successfully reaching and HIV testing >95% of elicited partners, newly diagnosing with HIV one in six of those tested, >90% of whom were linked to care. CLINICAL TRIAL NUMBER: NCT04774835.
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Infecções por HIV , Autoteste , Parceiros Sexuais , Humanos , Quênia , Masculino , Feminino , Infecções por HIV/diagnóstico , Adulto , Adulto Jovem , Pessoa de Meia-Idade , Adolescente , Teste de HIV/métodos , Teste de HIV/estatística & dados numéricosRESUMO
Downstream-of-gene (DoG) transcripts are an emerging class of noncoding RNAs. However, it remains largely unknown how DoG RNA production is regulated and whether alterations in DoG RNA signatures exist in major cancers. Here, through transcriptomic analyses of matched tumors and nonneoplastic tissues and cancer cell lines, we reveal a comprehensive catalog of DoG RNA signatures. Through separate lines of evidence, we support the biological importance of DoG RNAs in carcinogenesis. First, we show tissue-specific and stage-specific differential expression of DoG RNAs in tumors versus paired normal tissues with their respective host genes involved in tumor-promoting versus tumor-suppressor pathways. Second, we identify that differential DoG RNA expression is associated with poor patient survival. Third, we identify that DoG RNA induction is a consequence of treating colon cancer cells with the topoisomerase I (TOP1) poison camptothecin and following TOP1 depletion. Our results underlie the significance of DoG RNAs and TOP1-dependent regulation of DoG RNAs in diversifying and modulating the cancer transcriptome.
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Regulação Neoplásica da Expressão Gênica , Neoplasias , Transcriptoma , Humanos , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patologia , Linhagem Celular Tumoral , Perfilação da Expressão Gênica , DNA Topoisomerases Tipo I/metabolismo , DNA Topoisomerases Tipo I/genéticaRESUMO
BACKGROUND: Incentives have shown mixed results in increasing HIV testing rates in low-resource settings. We investigated the effectiveness of offering additional self-tests (HIVSTs) as an incentive to increase testing among partners receiving assisted partner services (APS). SETTING: Western Kenya. METHODS: We conducted a single-crossover study nested within a cluster-randomized controlled trial. Twenty-four facilities were randomized 1:1 to (1) control: provider-delivered testing or (2) intervention: offered 1 HIVST or provider-delivered testing for 6 months (pre-implementation), then switched to offering 2 HIVSTs for 6 months (post-implementation). A difference-in-differences approach using generalized linear mixed models, accounting for facility clustering and adjusting for age, sex, and income, was used to estimate the effect of the incentive on HIV testing and first-time testing among partners in APS. RESULTS: March 2021-June 2022, 1127 index clients received APS and named 8155 partners, among whom 2333 reported a prior HIV diagnosis and were excluded from analyses, resulting in 5822 remaining partners: 3646 (62.6%) and 2176 (37.4%) in the pre-implementation and post-implementation periods, respectively. Overall, 944/2176 partners (43%) were offered a second HIVST during post-preimplementation, of whom 34.3% picked up 2 kits, of whom 71.7% reported that the second kit encouraged HIV testing. Comparing partners offered 1 vs. two HIVSTs showed no difference in HIV testing (relative risk: 1.01, 95% confidence interval: 0.951 to 1.07) or HIV testing for the first time (relative risk: 1.23, 95% confidence interval: 0.671 to 2.24). CONCLUSIONS: Offering a second HIVST as an incentive within APS did not significantly impact HIV testing or first-time testing, although those opting for 2 kits reported it incentivized them to test.
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Infecções por HIV , Teste de HIV , Motivação , Autoteste , Humanos , Infecções por HIV/diagnóstico , Masculino , Feminino , Quênia , Adulto , Teste de HIV/métodos , Estudos Cross-Over , Pessoa de Meia-Idade , Adulto Jovem , Parceiros Sexuais , Adolescente , Programas de Rastreamento/métodosRESUMO
COVID-19 was the first pandemic of the internet age. Beginning at a time of great societal division in the United States (and globally), pandemic responses were further beleaguered by the viral proliferation of information, disinformation, and propaganda-collectively, an "infodemic." Polarized, blinkered views of the crisis precluded a balanced consideration of objectives, opportunities, and ineluctable trade-offs between the risks of actions and corresponding inactions. The results were lapses in both directions, greatly amplifying the pandemic toll. Persistence of this costly fractiousness is now spawning monocular critiques of the pandemic response, with neglect of essential nuance. There is a better pandemic that might have been, and the chance for far better responses to the next- but only if the follies of this history are lessons learned and applied. Failing that, the risk looms that having been amply forewarned of our liabilities, we will fail to be forearmed.
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Limited literature exists on chloramphenicol's clinical use. In this retrospective, single-center case-series, we examined 183 chloramphenicol-treated and 81 piperacillin-tazobactam-treated medical patients. Chloramphenicol recipients were older, more debilitated, cognitively impaired, and penicillin allergic, while increased need for inotropics, higher leukocyte count, and higher creatinine levels were notable in the piperacillin-tazobactam group. Pneumonia was the most common indication, with no mortality difference between groups. While acknowledging its antimicrobial activity and potential benefit in specific conditions such as pneumonia, further clinical studies are needed to assess the role of chloramphenicol in the setting where other alternatives are available.
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Antibacterianos , Cloranfenicol , Humanos , Cloranfenicol/uso terapêutico , Estudos Retrospectivos , Antibacterianos/uso terapêutico , Masculino , Idoso , Feminino , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Hospitalização/estatística & dados numéricos , Resultado do Tratamento , Combinação Piperacilina e Tazobactam/uso terapêutico , Adulto , DemografiaRESUMO
While pre-exposure prophylaxis (PrEP) has demonstrated efficacy in preventing HIV transmission, disparities in access persist in the United States, especially among Hispanic/Latinx sexual minority men (SMM). Language barriers and differences in how Latinx SMM obtain information may impact access to PrEP and HIV prevention. This study used data from the 2021 American Men's Internet Survey (AMIS) to examine differences in communication networks and PrEP use among Latinx SMM by primary language (Spanish vs. English). We examined the associations between Latinx SMM's individual- and meso-level communication networks and PrEP-related outcomes using modified Poisson regression with robust variances. Spanish-speaking Latinx SMM in the study were less likely to test for HIV, be aware of PrEP, and use daily PrEP, compared to English-speaking participants. Sexuality disclosure to a healthcare provider was positively associated with PrEP uptake among all participants and predicted STI testing over the past 12 months among English-speaking Latinx SMM. Findings highlight disparities in PrEP awareness and uptake among Latinx SMM, especially among those whose primary language is Spanish. Addressing these disparities through targeted interventions, including improved communication with healthcare providers, may help facilitate PrEP access and use in this population.
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Infecções por HIV , Hispânico ou Latino , Idioma , Profilaxia Pré-Exposição , Minorias Sexuais e de Gênero , Humanos , Masculino , Hispânico ou Latino/estatística & dados numéricos , Hispânico ou Latino/psicologia , Profilaxia Pré-Exposição/estatística & dados numéricos , Adulto , Infecções por HIV/prevenção & controle , Infecções por HIV/etnologia , Minorias Sexuais e de Gênero/estatística & dados numéricos , Minorias Sexuais e de Gênero/psicologia , Estados Unidos , Adulto Jovem , Pessoa de Meia-Idade , Adolescente , Inquéritos e Questionários , Barreiras de Comunicação , Comunicação , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/etnologia , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Conhecimentos, Atitudes e Prática em SaúdeRESUMO
INTRODUCTION: Many surgeons require patients to quit smoking prior to elective surgeries to reduce the risk of postoperative complications. Our aim was to qualitatively evaluate the communication and care experiences of patients and clinicians involved in conversations about quitting smoking prior to elective orthopaedic surgery. METHODS: A qualitative interview study of rural-residing Veterans, primary care providers (PCPs), and Veterans Administration (VA) orthopaedic surgery staff and pharmacists, who care for rural Veterans. We performed a combination of deductive and inductive approaches to support conventional content analysis using a Patient-Centered Care framework. RESULTS: Patients appreciated a shared approach with their PCP on the plan and reasons for cessation. Despite not knowing if the motivation for elective surgeries served as a teachable moment to facilitate long-term abstinence, almost all clinicians believed it typically helped in the short-term. There was a lack of standardized workflow between primary care and surgery, especially when patients used care delivered outside of VA. CONCLUSIONS: While clinician-provided information about the reasons behind the requirement to quit smoking preoperatively was beneficial, patients appreciated the opportunity to collaborate with their care teams on developing a plan for cessation and abstinence. Other aspects of patient-centered care need to be leveraged, such as the therapeutic alliance or patient-as-person, to build trust and improve communication surrounding tobacco use treatment. System-level changes may need to be made to improve coordination and connection of clinicians within and across disciplines. IMPLICATIONS: This study included perspectives from patients, primary care teams, and surgical teams and found that, in addition to providing information, clinicians need to address other aspects of patient-centered care such as the therapeutic alliance and patient-as-person domains to promote patient engagement in tobacco use treatment. This, in turn, could enhance the potential of surgery as a teachable moment and patient success in quitting smoking.
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Background: Persons seeking emergency injury care are often from underserved key populations (KPs) and priority populations (PPs) for HIV programming. While facility-based HIV Testing Services (HTS) in Kenya are effective, emergency department (ED) delivery is limited, despite the potential to reach underserved persons. Methods: This quasi-experimental prospective study evaluated implementation of the HIV Enhanced Access Testing in Emergency Departments (HEATED) at Kenyatta National Hospital ED in Nairobi, Kenya. The HEATED program was designed using setting specific data and utilizes resource reorganization, services integration and HIV sensitization to promote ED-HTS. KPs included sex workers, gay men, men who have sex with men, transgender persons and persons who inject drugs. PPs included young persons (18-24 years), victims of interpersonal violence, persons with hazardous alcohol use and those never previously HIV tested. Data were obtained from systems-level records, enrolled injured patient participants and healthcare providers. Systems and patient-level data were collected during a pre-implementation period (6 March - 16 April 2023) and post-implementation (period 1, 1 May - 26 June 2023). Additional, systems-level data were collected during a second post-implementation (period 2, 27 June - 20 August 2023). Evaluation analyses were completed across reach, effectiveness, adoption, implementation and maintenance framework domains. Results: All 151 clinical staff were reached through trainings and sensitizations on the HEATED program. Systems-level ED-HTS increased from 16.7% pre-implementation to 23.0% post-implementation periods 1 and 2 (RR=1.31, 95% CI:1.21-1.43; p<0.001) with a 62.9% relative increase in HIV self-test kit provision. Among 605 patient participants, facilities-based HTS increased from 5.7% pre-implementation to 62.3% post-implementation period 1 (RR=11.2, 95%CI:6.9-18.1; p<0.001). There were 440 (72.7%) patient participants identified as KPs (5.6%) and/or PPs (65.3%). For enrolled KPs/PPs, HTS increased from 4.6% pre-implementation to 72.3% post-implementation period 1 (RR=13.8, 95%CI:5.5-28.7, p<0.001). Systems and participant level data demonstrated successful adoption and implementation of the HEATED program. Through 16-weeks post-implementation a significant increase in ED-HTS delivery was maintained as compared to pre-implementation. Conclusions: The HEATED program increased ED-HTS and augmented delivery to KPs/PPs, suggesting that broader implementation could improve HIV services for underserved persons, already in contact with health systems.
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Objective: To compare preferences, uptake, and cofactors for unassisted home-based oral self-testing (HB-HIVST) versus clinic-based rapid diagnostic blood tests (CB-RDT) for maternal HIV retesting. Design: Prospective cohort. Methods: Between November 2017 and June 2019, HIV-negative pregnant Kenyan women receiving antenatal care were enrolled and given a choice to retest with HB-HIVST or CB-RDT. Women were asked to retest between 36 weeks gestation and 1 week post-delivery if the last HIV test was <24 weeks gestation or at 6 weeks postpartum if ≥24 weeks gestation, and self-report on retesting at a 14 week postpartum. Results: Overall, 994 women enrolled and 33% (n=330) selected HB-HIVST. HB-HIVST was selected because it was private (68%), convenient (63%), and offered flexibility in timing of retesting (63%), whereas CB-RDT was selected due to trust of providers to administer the test (77%) and convenience of clinic testing (64%). Among 905 women who reported retesting at follow-up, 135 (15%) used HB-HIVST. Most (94%) who selected CB-RDT retested with this strategy, compared to 39% who selected HB-HIVST retesting with HB-HIVST. HB-HIVST retesting was more common among women with higher household income and those who may have been unable to test during pregnancy (both retested postpartum and delivered <37 weeks gestation) and less common among women who were depressed. Most women said they would retest in the future using the test selected at enrollment (99% HB-HIVST; 93% CB-RDT-RDT). Conclusions: While most women preferred CB-RDT for maternal retesting, HB-HIVST was acceptable and feasible and may increase retesting coverage and partner testing.
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Ethyl cellulose-ethanol (ECE) is emerging as a promising formulation for ablative injections, with more controllable injection distributions than those from traditional liquid ethanol. This study evaluates the influence of salient injection parameters on forces needed for infusion, depot volume, retention, and shape in a large animal model relevant to human applications. Experiments were conducted to investigate how infusion volume (0.5 mL to 2.5 mL), ECE concentration (6% or 12%), needle gauge (22 G or 27 G), and infusion rate (10 mL/h) impacted the force of infusion into air using a load cell. These parameters, with the addition of manual infusion, were investigated to elucidate their influence on depot volume, retention, and shape (aspect ratio), measured using CT imaging, in an ex vivo swine liver model. Force during injection increased significantly for 12% compared to 6% ECE and for 27 G needles compared to 22 G. Force variability increased with higher ECE concentration and smaller needle diameter. As infusion volume increased, 12% ECE achieved superior depot volume compared to 6% ECE. For all infusion volumes, 12% ECE achieved superior retention compared to 6% ECE. Needle gauge and infusion rate had little influence on the observed depot volume or retention; however, the smaller needles resulted in higher variability in depot shape for 12% ECE. These results help us understand the multivariate nature of injection performance, informing injection protocol designs for ablations using gel ethanol and infusion, with volumes relevant to human applications.
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Leber hereditary optic neuropathy (LHON) is a mitochondrial disease leading to rapid and severe bilateral vision loss. Idebenone has been shown to be effective in stabilizing and restoring vision in patients treated within 1 year of onset of vision loss. The open-label, international, multicenter, natural history-controlled LEROS study (ClinicalTrials.gov NCT02774005) assesses the efficacy and safety of idebenone treatment (900 mg/day) in patients with LHON up to 5 years after symptom onset (N = 199) and over a treatment period of 24 months, compared to an external natural history control cohort (N = 372), matched by time since symptom onset. LEROS meets its primary endpoint and confirms the long-term efficacy of idebenone in the subacute/dynamic and chronic phases; the treatment effect varies depending on disease phase and the causative mtDNA mutation. The findings of the LEROS study will help guide the clinical management of patients with LHON.
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Atrofia Óptica Hereditária de Leber , Ubiquinona/análogos & derivados , Humanos , Atrofia Óptica Hereditária de Leber/tratamento farmacológico , Atrofia Óptica Hereditária de Leber/genética , Atrofia Óptica Hereditária de Leber/diagnóstico , Antioxidantes/uso terapêutico , Ubiquinona/uso terapêutico , Ubiquinona/genética , MutaçãoRESUMO
Desalination can reduce both water scarcity and variability in supplies, two factors identified as drivers of transboundary water conflict. As such, some have predicted that increasing development of desalination capacity may reduce conflict over shared waters. Others have claimed that desalination may become a source of new conflicts. Additionally, desalination may open up new avenues for cooperation, but also may allow for unilateral action by parties, thereby decreasing cooperation. This study looks at the impact of the introduction of desalination on hydro-political relations in two protracted conflict settings: the island of Cyprus and the Arab-Israeli conflict. Using both quantitative and qualitative assessments, we find that desalination has fundamentally altered hydro-political relations, but find no consistent trends in terms of levels of conflict and cooperation. These findings suggest that the influence of desalination on hydro-political relations is likely to be a function of, rather than a transformer of, the larger geopolitical context.
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Abastecimento de Água , Água , Humanos , ÁrabesRESUMO
The Single-Port (SP) robotic system is increasingly being implemented in the United States, allowing for several minimally invasive urologic procedures to be performed. The present study aims to describe our single-center experience since the adoption of the SP platform. We retrospectively collected and analyzed consecutive SP cases performed at a major teaching hospital in the Midwest (Rush University Medical Center) from December 2020 to December 2023. Demographic variables were collected. Surgical and pathological outcomes were analyzed in the overall cohort and for each type of procedure. The study timeframe was divided into two periods to assess the evolution of SP technical features over time. In total, 160 procedures were performed, with robot-assisted radical prostatectomy (RARP) being the most common (49.4%). Overall, 54.4% of the procedures were extraperitoneal, with a significantly higher adoption of this approach in the second half of the study period (30% vs 74.3%, p < 0.001). A "plus one" assistant port was adopted in 38.1% of cases, with a shift towards a "pure" single-port surgery in the most recent procedures (21.1% vs 76.7%, p < 0.001). The median LOS was 33.5 h (30-48), with a rate of any grade and CD ≥ 3 postoperative complications of 9.4% and 2.5%, respectively, and a 30-day readmission rate of 1.9%. SP robotic surgery can be safely and effectively implemented for various urologic procedures. With increasing experience, the SP platform allows shifting away from transperitoneal procedures, potentially minimizing postoperative pain, and shortening hospital stay and postoperative recovery.
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Procedimentos Cirúrgicos Robóticos , Robótica , Masculino , Humanos , Procedimentos Cirúrgicos Robóticos/métodos , Estudos Retrospectivos , Procedimentos Cirúrgicos Urológicos , Prostatectomia/métodosRESUMO
Analysis of DNA methylation in cell-free DNA reveals clinically relevant biomarkers but requires specialized protocols such as whole-genome bisulfite sequencing. Meanwhile, millions of cell-free DNA samples are being profiled by whole-genome sequencing. Here, we develop FinaleMe, a non-homogeneous Hidden Markov Model, to predict DNA methylation of cell-free DNA and, therefore, tissues-of-origin, directly from plasma whole-genome sequencing. We validate the performance with 80 pairs of deep and shallow-coverage whole-genome sequencing and whole-genome bisulfite sequencing data.
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Ácidos Nucleicos Livres , Metilação de DNA , Metilação de DNA/genética , Sequenciamento Completo do Genoma/métodos , Sulfitos , Ácidos Nucleicos Livres/genética , Análise de Sequência de DNA/métodos , Sequenciamento de Nucleotídeos em Larga EscalaRESUMO
The UK Research Excellence Framework (REF) is an assessment of the quality of research carried out in UK Higher Education Institutions (HEIs), performed in 7-year cycles. The outcome impacts the rankings and funding of UK HEIs, which afford the exercise high priority. Much of what REF measures is known to be biased against academics with protected characteristics: for example, women and ethnic minority researchers are less likely to win grants or be published in prestigious journals. Despite changes to REF since 2014, the risk remains that the process might amplify well-recognised existing disparities. The BMA Women in Academic Medicine and Medical Academic Staff Committee carried out a survey of UK clinical academics' experiences of REF2021. The data indicated the persistence of activities previously characterised as 'extremely harmful' in Research England-commissioned work, affecting up to 10% of clinical academics. While acknowledging the limitations of the data, women appeared to be disproportionately affected.
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Etnicidade , Grupos Minoritários , Humanos , Feminino , Inglaterra , Exercício Físico , Corpo ClínicoRESUMO
This study measures changes in condomless anal sex (CAS) among HIV-negative men who have sex with men (MSM) who are not taking pre-exposure prophylaxis (PrEP). It considers the 2014-2019 cycles of the American Men's Internet Survey, a serial, cross-sectional web-based survey of US cisgender MSM aged ≥ 15 years, in which ~ 10% of each year's sample is drawn from the previous year. Among those surveyed for 2 years who remained HIV-negative and off PrEP, reports of having any CAS and of CAS partner number were compared across years. We disaggregated by partner HIV status, and considered demographic predictors. The overall population saw a significant 2.2 percentage-point (pp) increase in reports of any CAS year-over-year. Sub-populations with the largest year-on-year increases were 15-24-year-olds (5.0-pp) and Hispanic respondents (5.1-pp), with interaction (young Hispanic respondents = 12.8-pp). On the relative scale, these numbers correspond to 3.2%, 7.2%, 7.3% and 18.7%, respectively. Absolute increases were concentrated among partners reported as HIV-negative. Multivariable analyses for CAS initiation found effects concentrated among Hispanic and White youth and residents of fringe counties of large metropolitan areas. CAS partner number increases were similarly predicted by Hispanic identity and young age. Although condom use remains more common than PrEP use, increasing CAS among MSM not on PrEP suggests potential new HIV transmission pathways. Concentration of increases among 18-24-year-old MSM portends future increases in the proportion of newly diagnosed HIV that occur among youth. Concentration among young Hispanic MSM will likely expand existing disparities. Although reducing barriers to PrEP remains vital, condom promotion for MSM remains a key public health practice and appears to be missing key audiences. LGBTQ+-inclusive sex education is one avenue for enhancing these efforts.
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Preservativos , Infecções por HIV , Homossexualidade Masculina , Profilaxia Pré-Exposição , Parceiros Sexuais , Sexo sem Proteção , Adolescente , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Preservativos/estatística & dados numéricos , Estudos Transversais , Hispânico ou Latino/estatística & dados numéricos , Hispânico ou Latino/psicologia , Infecções por HIV/prevenção & controle , Infecções por HIV/epidemiologia , Soronegatividade para HIV , Homossexualidade Masculina/estatística & dados numéricos , Homossexualidade Masculina/psicologia , Profilaxia Pré-Exposição/estatística & dados numéricos , Assunção de Riscos , Minorias Sexuais e de Gênero/estatística & dados numéricos , Minorias Sexuais e de Gênero/psicologia , Comportamento Sexual/estatística & dados numéricos , Inquéritos e Questionários , Estados Unidos/epidemiologia , Sexo sem Proteção/estatística & dados numéricos , Sexo sem Proteção/psicologia , BrancosRESUMO
Lifestyle Medicine (LM) is a rapidly growing discipline that focuses on the role of lifestyle factors in preventing, managing, and reversing chronic disease. At this point in the field's evolution, there is strong evidence that the 6 pillars of LM-a whole-food, plant-predominant eating pattern, physical activity, restorative sleep, stress management, avoidance of risky substances, and positive social connections-are central in the creation and maintenance of health. Previous publications, many of them randomized controlled studies and meta-analyses, have solidified the evidence base for the use of the 6 pillars within the field of LM. As data emerged, so did its governing body, the American College of Lifestyle Medicine (ACLM), and with it a rich history began to unfold. Several articles have been written on the early history of the ACLM and the growth of the field; however, this review article explores the history and foundation of LM, aiming to provide a comprehensive understanding of its relevance and impact on health care. It underscores landmark studies that have defined the field and provides a road map detailing national and global barriers and areas of potential future growth.