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Pre-exposure prophylaxis (PrEP) is effective in preventing HIV transmission, but uptake and adherence among young men who have sex with men (YMSM) remains suboptimal. New PrEP formulations may enhance PrEP use, but little is known about their acceptability. We enrolled 39 cis- and transgender YMSM (age 18-34) from Boston, MA; Jackson, MS; Birmingham, AL; and New Orleans, LA, who participated in video-based focus groups (n = 30) or in-depth interviews (n = 9) to examine how new PrEP products (e.g., injections, monthly pills, implants) are perceived and might be improved for YMSM. Focus groups were transcribed, coded, and analyzed using grounded theory and content analysis. Nearly half (46%) of participants were Black; 11% identified as Hispanic. Seventy-nine percent were PrEP experienced. Product preference was driven by the desire for flexible, safe, effective, and affordable PrEP options. A majority of participants preferred subcutaneous injections every 6 months or monthly pills dispersed in 3 or 4 doses. Subcutaneous injections and batched monthly pills were favored by those with demanding schedules and those who desired fewer provider visits; monthly pills were more appealing for those who feared needles. Despite broad preferences for longer-acting products for convenience, participants raised concerns regarding side effects and waning protection after missed doses. Participants felt that more education about safety and efficacy profiles of new products could influence their attitudes. These findings suggest that it is important to prioritize YMSM's dynamic lifestyles during product development, and that product safety and efficacy information should be accessible in youth-friendly language.
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Despite its effectiveness in HIV prevention, PrEP use among Black women is suboptimal. Notably in the Deep South, Black women have the lowest PrEP uptake rates among all US regions. To increase PrEP engagement, research suggests the implementation of structural and social interventions particular to the needs of Black women. The state of Alabama is of priority to federal HIV prevention initiatives; therefore, this study conducted focus groups among 47 cis-gender Black women in rural and urban Alabama counties, with the highest statewide HIV incidence rates, to understand perceptions of PrEP and decision-making processes. Deductive coding analysis was conducted and themes were finalized based on consensus among the two coders. Four themes were identified. Findings show stigma undergirds Alabaman Black women's decisions to engage in PrEP care. Moreover, women reported stigma stifled community-level education about PrEP. Despite these experiences, education was regarded as a strategy to decrease stigma and PrEP skepticism, the latter of which emerged as a prominent theme. Medical mistrust and healthcare engagement were the other emergent themes influencing participation in PrEP care. To ensure PrEP efforts meet the needs of Black cisgender women in Alabama counties, interventions must address longstanding stigma, increase educational initiatives, and ensure interventions consider women's experiences with medical mistrust and health care engagement.
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Infecções por HIV , Profilaxia Pré-Exposição , Humanos , Feminino , Confiança , Negro ou Afro-Americano , Infecções por HIV/prevenção & controle , População NegraRESUMO
BACKGROUND: Black cisgender women (CGW) are disproportionately impacted by the human immunodeficiency virus (HIV) epidemic in the United States. Black women account for 57% of the total new diagnoses among CGW. In addition, Black CGW women are 9 times more likely to be diagnosed with HIV than their White counterparts. METHODS: We conducted surveys (September 2019-March 2020) and collected information on sociodemographics, HIV/preexposure prophylaxis (PrEP) knowledge, HIV/PrEP stigma, sexual practices, and other factors identified as PrEP barriers among Black CGW (n = 795). This cross-sectional study used logistic regression models to assess intrapersonal, interpersonal, and structural factors among individuals willing to use PrEP versus individuals unwilling or unsure to use PrEP. RESULTS: Our study population had a mean age of 37 years, predominantly lived in urban areas (65%), had stable housing (96.7%), and had private insurance/Medicare (78.2%). Overall, 29.6% reported willingness to use PrEP, 35.6% reported unwillingness to use PrEP, and 34.8% were unsure of PrEP use. The multivariable analysis showed that, compared with individuals reporting unwillingness/unsure to PrEP use, those reporting willingness to PrEP use were younger (adjusted odds ratio [AOR; 95% confidence interval {CI}], 0.97 [0.96-0.99]), had lower odds of intimate partner violence (AOR [95% CI], 0.87 [0.78-0.98), and had higher odds of organizational religiosity (AOR [95% CI], 1.10 [1.01-1.20]), HIV knowledge (AOR [95% CI], 1.08 [1.03-1.13]), and perceived need for PrEP (AOR [95% CI], 6.38 [3.36-12.11]). CONCLUSIONS: Preexposure prophylaxis willingness among Black CGW was impacted by individual-level, interpersonal, and structural factors. Improving PrEP willingness and uptake among Black CGW will require multilevel interventions.
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To assess PrEP service delivery preferences among Black cis-gender women living in urban and rural settings in Alabama, we conducted a cross-sectional discrete choice experiment survey. Discrete choice experiments included five attributes. Hierarchical Bayes (HB) modeling and latent class analyses (LCA) were used to evaluate attribute preferences. Among 795 Black cis-gender HIV-negative women, almost two-thirds lived in urban settings and reported having at least some college; about a third reported a household income less than $25,000 annually; and reported willingness to use PrEP. Respondents placed the greatest importance on PrEP medication formulation and healthcare facility. LCA showed the group with the highest rural proportion preferred for on-line visits. Black women in the Deep South had distinct preferences regarding PrEP service delivery. These findings can inform tailored interventions to improve PrEP uptake among Black cis-gender women across diverse settings in the South.
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Fármacos Anti-HIV , Infecções por HIV , Profilaxia Pré-Exposição , Fármacos Anti-HIV/uso terapêutico , Teorema de Bayes , População Negra , Estudos Transversais , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Humanos , Estados UnidosRESUMO
Understanding resilience in relation to HIV-related outcomes may help address racial/ethnic disparities, however, significant gaps in its measurement preclude in-depth study. Thus, this research aims to develop and evaluate the psychometric properties of long and short forms of the Multilevel Resilience Resource Measure for African American/Black Adults Living with HIV. To develop the items, we conducted a mixed methods study (N = 48) and reviewed published resilience measures. We completed content validity index analyses to ensure the items reflected the resilience construct. Next, we conducted 20 cognitive interviews and a field survey (N = 400). The long and short forms demonstrated acceptable to excellent psychometric properties based on factorial validity, internal consistency and convergent validity and on measurement invariance (conducted for the short form only). These measures provide a comprehensive framework to examine resilience and HIV-related outcomes and can inform resilience-building interventions to reduce racial and ethnic health disparities.
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Negro ou Afro-Americano , Infecções por HIV , Adulto , Negro ou Afro-Americano/psicologia , População Negra , Infecções por HIV/psicologia , Humanos , Psicometria , Grupos Raciais , Reprodutibilidade dos Testes , Inquéritos e QuestionáriosRESUMO
Resilience may help people living with HIV (PLWH) overcome adversities to disease management. This study identifies multilevel resilience resources among African American/Black (AA/B) PLWH and examines whether resilience resources differ by demographics and neighborhood risk environments. We recruited participants and conducted concept mapping at two clinics in the southeastern United States. Concept Mapping incorporates qualitative and quantitative methods to represent participant-generated concepts via two-dimensional maps. Eligible participants had to attend ≥ 75% of their scheduled clinic appointments and did not have ≥ 2 consecutive detectable HIV-1 viral load measurements in the past 2 years. Of the 85 AA/B PLWH who were invited, forty-eight participated. Twelve resilience resource clusters emerged-five individual, two interpersonal, two organizational/policy and three neighborhood level clusters. There were strong correlations in cluster ratings for demographic and neighborhood risk environment comparison groups (r ≥ 0.89). These findings could inform development of theories, measures and interventions for AA/B PLWH.
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Negro ou Afro-Americano/psicologia , Infecções por HIV/psicologia , Equidade em Saúde , Resiliência Psicológica , Adulto , Fármacos Anti-HIV/uso terapêutico , População Negra/psicologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/etnologia , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multinível , Características de Residência , Sudeste dos Estados Unidos/epidemiologiaRESUMO
PURPOSE: To investigate the role of patient-specific dosimetry as a predictive marker of survival and as a potential tool for individualised molecular radiotherapy treatment planning of bone metastases from castration-resistant prostate cancer, and to assess whether higher administered levels of activity are associated with a survival benefit. METHODS: Clinical data from 57 patients who received 2.5-5.1 GBq of 186Re-HEDP as part of NIH-funded phase I/II clinical trials were analysed. Whole-body and SPECT-based absorbed doses to the whole body and bone lesions were calculated for 22 patients receiving 5 GBq. The patient mean absorbed dose was defined as the mean of all bone lesion-absorbed doses in any given patient. Kaplan-Meier curves, log-rank tests, Cox's proportional hazards model and Pearson's correlation coefficients were used for overall survival (OS) and correlation analyses. RESULTS: A statistically significantly longer OS was associated with administered activities above 3.5 GBq in the 57 patients (20.1 vs 7.1 months, hazard ratio: 0.39, 95 % CI: 0.10-0.58, P = 0.002). A total of 379 bone lesions were identified in 22 patients. The mean of the patient mean absorbed dose was 19 (±6) Gy and the mean of the whole-body absorbed dose was 0.33 (±0.11) Gy for the 22 patients. The patient mean absorbed dose (r = 0.65, P = 0.001) and the whole-body absorbed dose (r = 0.63, P = 0.002) showed a positive correlation with disease volume. Significant differences in OS were observed for the univariate group analyses according to disease volume as measured from SPECT imaging of 186Re-HEDP (P = 0.03) and patient mean absorbed dose (P = 0.01), whilst only the disease volume remained significant in a multivariable analysis (P = 0.004). CONCLUSION: This study demonstrated that higher administered activities led to prolonged survival and that for a fixed administered activity, the whole-body and patient mean absorbed doses correlated with the extent of disease, which, in turn, correlated with survival. This study shows the importance of patient stratification to establish absorbed dose-response correlations and indicates the potential to individualise treatment of bone metastases with radiopharmaceuticals according to patient-specific imaging and dosimetry.
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Ácido Etidrônico/administração & dosagem , Compostos Organometálicos/administração & dosagem , Neoplasias de Próstata Resistentes à Castração/radioterapia , Doses de Radiação , Compostos Radiofarmacêuticos/administração & dosagem , Planejamento da Radioterapia Assistida por Computador , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/secundário , Ensaios Clínicos Fase I como Assunto , Ensaios Clínicos Fase II como Assunto , Ácido Etidrônico/uso terapêutico , Humanos , Masculino , Compostos Organometálicos/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/diagnóstico por imagem , Neoplasias de Próstata Resistentes à Castração/patologia , Compostos Radiofarmacêuticos/uso terapêutico , Dosagem Radioterapêutica , Análise de Sobrevida , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
OBJECTIVE: Describe chest and abdominal injury epidemiology among US high school athletes. DESIGN: Retrospective analysis of longitudinal surveillance data. SETTING: Injury data from 2005/06 to 2013/14 academic years were collected using an internet-based surveillance system. PARTICIPANTS: A large sample of US high schools. ASSESSMENT OF RISK FACTORS: Injuries sustained as a function of sport. MAIN OUTCOME MEASURES: Chest, rib, thoracic spine, and abdominal injuries sustained during high school athletic events. RESULTS: Overall 1487 chest, rib, thoracic spine, and abdominal injuries occurred during 30 415 179 athletic exposures (AEs); an injury rate of 4.9 injuries per 100 000 AEs. Over half (56.8%) of injured athletes were evaluated by another medical provider in addition to the athletic trainer, and 34 injuries (2.3%) required surgery. Diagnostic techniques, including x-ray, magnetic resonance imaging or computed tomography were used in 729 (49.0%) injuries. The injury rate was higher in boys' (6.8) than girls' (2.0) sports [rate ratio (RR), 3.43; 95% CI, 3.04-4.10]. Football (47.7%) accounted for the highest proportion of injuries followed by wrestling (18.5%), boys' soccer (4.6%), and girls' soccer (3.7%). The rate of injury was higher in competition than practice, (RR, 2.86; 95% CI, 2.59-3.23). Only 57.7% of injured athletes were able to return to play within 1 week. CONCLUSIONS: Chest and abdominal injuries in high school sports although relatively rare, can result in loss of playing time and frequently prompt medical evaluation. Thus, they present a physical and economic burden. To optimize prevention, further studies can focus on subgroup risk factor identification to drive development of targeted prevention strategies.
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Traumatismos Abdominais/epidemiologia , Traumatismos em Atletas/epidemiologia , Costelas/lesões , Traumatismos da Coluna Vertebral/epidemiologia , Traumatismos Torácicos/epidemiologia , Adolescente , Atletas , Feminino , Futebol Americano/lesões , Humanos , Estudos Longitudinais , Masculino , Estudos Retrospectivos , Instituições Acadêmicas , Futebol/lesões , Estados Unidos/epidemiologia , Luta Romana/lesõesRESUMO
ABSTRACT: The second victim phenomenon describes the distress frequently experienced by health care providers after an unintentional medical error or unexpected adverse event. However, few health care institutions have initiatives that proactively address this phenomenon. The pilot project discussed in this article aimed to create a peer support program for health care providers experiencing the second victim phenomenon. The project team validated the need for such a program among health care providers in the perioperative departments of two facilities within a large health care organization in the southeastern United States. To do this, they used a survey, the Second Victim Experience and Support Tool. Among survey respondents in the two departments, 80% and 87.6% indicated a strong desire to discuss their emotional challenges with a respected peer colleague after a traumatic event. The project team then developed and implemented a peer support program in three phases to 1) educate staff across the facility on second victimization, 2) recruit and train volunteer peer supporters, and 3) launch the pilot program by embedding these peer supporters in the two perioperative departments. A survey completed by participants in the pilot program showed that 80% of respondents found the peer support extremely beneficial, 20% found it very beneficial, and 100% would recommend peer support to a colleague. This successful pilot project could inform the establishment of peer support programs at other institutions to assist health care providers experiencing the second victim phenomenon.
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Grupo Associado , Apoio Social , Humanos , Projetos Piloto , Erros Médicos/prevenção & controle , Inquéritos e Questionários , Feminino , Masculino , Pessoal de Saúde/psicologia , Sudeste dos Estados Unidos , AdultoRESUMO
OBJECTIVE: To assess overall and by neighborhood risk environments whether multilevel resilience resources were associated with HIV virologic suppression among African American/Black adults in the Southeastern United States. SETTING AND METHODS: This clinical cohort sub-study included 436 African American/Black participants enrolled in two parent HIV clinical cohorts. Resilience was assessed using the Multilevel Resilience Resource Measure (MRM) for African American/Black adults living with HIV, where endorsement of a MRM statement indicated agreement that a resilience resource helped a participant continue HIV care despite challenges or was present in a participant's neighborhood. Modified Poisson regression models estimated adjusted prevalence ratios (aPRs) for virologic suppression as a function of categorical MRM scores, controlling for demographic, clinical, and behavioral characteristics at or prior to sub-study enrollment. We assessed for effect measure modification (EMM) by neighborhood risk environments. RESULTS: Compared to participants with lesser endorsement of multilevel resilience resources, aPRs for virologic suppression among those with greater or moderate endorsement were 1.03 (95% confidence interval: 0.96-1.11) and 1.03 (0.96-1.11), respectively. Regarding multilevel resilience resource endorsement, there was no strong evidence for EMM by levels of neighborhood risk environments. CONCLUSIONS: Modest positive associations between higher multilevel resilience resource endorsement and virologic suppression were at times most compatible with the data. However, null findings were also compatible. There was no strong evidence for EMM concerning multilevel resilience resource endorsement, which could have been due to random error. Prospective studies assessing EMM by levels of the neighborhood risk environment with larger sample sizes are needed.
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Infecções por HIV , Resiliência Psicológica , Adulto , Humanos , Estados Unidos , Negro ou Afro-Americano , Estudos Prospectivos , Sudeste dos Estados Unidos , Infecções por HIV/tratamento farmacológico , Características de ResidênciaRESUMO
Importance: Chronic pain is a common condition for which efficacious interventions tailored to highly affected populations are urgently needed. People with HIV have a high prevalence of chronic pain and share phenotypic similarities with other highly affected populations. Objective: To evaluate the efficacy of a behavioral pain self-management intervention called Skills to Manage Pain (STOMP) compared to enhanced usual care (EUC). Design, Setting, and Participants: This randomized clinical trial included adults with HIV who experienced at least moderate chronic pain for 3 months or more. The study was set at the University of Alabama at Birmingham and the University of North Carolina-Chapel Hill large medical centers from August 2019 to September 2022. Intervention: STOMP combined 1-on-1 skill-building sessions delivered by staff interventionists with group sessions co-led by peer interventionists. The EUC control group received the STOMP manual without any 1-on-1 or group instructional sessions. Main Outcomes and Measures: The primary outcome was pain severity and the impact of pain on function, measured by the Brief Pain Inventory (BPI) summary score. The primary a priori hypothesis was that STOMP would be associated with a decreased BPI in people with HIV compared to EUC. Results: Among 407 individuals screened, 278 were randomized to STOMP intervention (n = 139) or EUC control group (n = 139). Among the 278 people with HIV who were randomized, the mean (SD) age was 53.5 (10.0) years; 126 (45.0%) identified as female, 146 (53.0%) identified as male, 6 (2.0%) identified as transgender female. Of the 6 possible 1-on-1 sessions, participants attended a mean (SD) of 2.9 (2.5) sessions. Of the 6 possible group sessions, participants attended a mean (SD) of 2.4 (2.1) sessions. Immediately after the intervention compared to EUC, STOMP was associated with a statistically significant mean difference for the primary outcome, BPI total score: -1.25 points (95% CI, -1.71 to -0.78 points; P < .001). Three months after the intervention, the mean difference in BPI total score remained statistically significant, favoring the STOMP intervention -0.62 points (95% CI, -1.09 to -0.14 points; P = .01). Conclusion and Relevance: The findings of this randomized clinical trial support the efficaciousness of STOMP as an intervention for chronic pain in people with HIV. Future research will include implementation studies and work to understand the optimal delivery of the intervention. Trial Registration: ClinicalTrials.gov Identifier: NCT03692611.
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The Gulf pipefish Syngnathus scovelli has emerged as an important species for studying sexual selection, development, and physiology. Comparative evolutionary genomics research involving fishes from Syngnathidae depends on having a high-quality genome assembly and annotation. However, the first S. scovelli genome assembled using short-read sequences and a smaller RNA-sequence dataset has limited contiguity and a relatively poor annotation. Here, using PacBio long-read high-fidelity sequences and a proximity ligation library, we generate an improved assembly to obtain 22 chromosome-level scaffolds. Compared to the first assembly, the gaps in the improved assembly are smaller, the N75 is larger, and our genome is ~95% BUSCO complete. Using a large body of RNA-Seq reads from different tissue types and NCBI's Eukaryotic Annotation Pipeline, we discovered 28,162 genes, of which 8,061 are non-coding genes. Our new genome assembly and annotation are tagged as a RefSeq genome by NCBI and provide enhanced resources for research work involving S. scovelli..
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The prolonged COVID-19 pandemic has created unique and complex challenges in operational and capacity planning for pediatric emergency departments, as initial low pediatric patient volumes gave way to unpredictable patient surges during Delta and Omicron variants. Compounded by widespread hospital supply chain issues, staffing shortages due to infection and attrition, and a concurrent pediatric mental health crisis, the surges have pushed pediatric emergency department leaders to re-examine traditionally defined clinical processes, and adopt innovative operational strategies. This study describes the strategic surge response and lessons learned by 3 major freestanding academic pediatric emergency departments in the western United States to help inform current and future pediatric pandemic preparedness.
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COVID-19 , Humanos , Criança , COVID-19/epidemiologia , Pandemias/prevenção & controle , SARS-CoV-2 , Serviço Hospitalar de EmergênciaRESUMO
BACKGROUND: The syndemic of mental health (MH) and substance use disorders (SUDs) is common among persons living with HIV and jeopardizes HIV treatment adherence, engagement in care, and viral load suppression. Electronic patient-reported outcomes (ePROs), completed through tablet or computer, and telemedicine are evidence- and technology-based interventions that have been used to successfully increase screening and treatment, respectively, a model that holds promise for persons living with HIV. To date, there is limited guidance on implementing ePROs and telemedicine into HIV clinical practice even though it is well known that these evidence-based tools improve diagnosis and access to care. OBJECTIVE: To address this, we aim to conduct a multicomponent intervention for persons living with HIV, including the delivery of HIV services and telemedicine through effective ePROs (+STEP), to increase screening and treatment of MH and SUD in Ryan White HIV/AIDS Program (RWHAP)-funded clinics in Alabama. METHODS: Through this intervention, we will conduct a readiness, acceptability, and accessibility assessment and implement +STEP to improve the diagnosis and treatment of MH and SUD at RWHAP clinics in Alabama. To describe implementation strategies that address barriers to the uptake of +STEP in RWHAP clinics, we will conduct qualitative interviews in years 1 (early implementation), 2 (scale up), and 4 (maintenance) with patients and key staff to evaluate barriers, facilitators, and implementation strategies. Our Results will enable us to modify strategies to enhance +STEP penetration over time and inform the implementation blueprint, which we will develop for both RWHAP clinics in Alabama and future sites. We will assess the impact of implementing +STEP on diagnoses, referrals, and health care use related to MH, SUD, and HIV by comparing clinical outcomes from patients receiving these interventions (ePROs and telemedicine) with historical controls. RESULTS: The first study site began implementation in April 2022. A total of 2 additional sites have initiated ePROs. Final results are expected in 2026. The results of this study will provide a foundation for future research expanding access to ePROs for improved diagnosis linked to telemedicine access to accelerate patients along the continuum of care from MH and SUD diagnosis to treatment. CONCLUSIONS: Achieving the end of the HIV epidemic in the United States necessitates programs that accelerate movement across the MH and SUD care continuum from diagnosis to treatment for persons living with HIV. Scaling these services represents a path toward improved treatment outcomes with both individual health and population-level prevention benefits of sustained HIV viral suppression in the era of undetectable=untransmittable (U=U). This study will address this evidence gap through the evaluation of the implementation of +STEP to establish the necessary systems and processes to screen, identify, and better treat substance use and MH for people living with HIV. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/40470.
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BACKGROUND: Behavioral interventions for chronic pain among people with HIV (PWH) are understudied, with great potential to improve pain and function. Chronic pain is an important comorbidity that affects between 30% and 85% of PWH and is associated with greater odds of functional impairment, increased emergency room utilization, suboptimal retention in HIV care, and failure to achieve virologic suppression. However, to date, there are few effective and scalable interventions for chronic pain in PWH. OBJECTIVE: This manuscript outlines the protocol for a randomized control trial of a novel theory-based pain self-management intervention, "Skills TO Manage Pain" (STOMP), developed for and tailored to PWH versus enhanced usual care controls. STOMP is a 12-week intervention developed from prior work on pain self-management in PWH and rigorous intervention mapping. The STOMP intervention has three major components: group sessions, one-on-one pain self-management sessions, and peer leaders. METHODS: STOMP is a 2-arm randomized trial conducted with PWH with chronic pain. The trial compares STOMP, a theory-based intervention tailored to improving chronic pain in PWH, with a comparison group receiving enhanced usual care effectiveness on pain and HIV proximal outcome measures. The proposed sample size is 280 PWH recruited from two high-volume Center for AIDS Research Network of Integrated Clinical Systems clinical sites. RESULTS: Study procedures are ongoing, and results will be recorded in future manuscripts. CONCLUSION: The study will generate evidence on the effectiveness of STOMP with the potential to dramatically change chronic pain treatment for PWH. TRIAL REGISTRATION: clinicialtrials.gov, Clinical Trials Registration # NCT03692611https://clinicaltrials.gov/ct2/show/NCT03692611?term=STOMP&cond=Hiv&draw=2&rank=1.
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Dor Crônica , Infecções por HIV , Autogestão , Humanos , Dor Crônica/terapia , Dor Crônica/epidemiologia , Comorbidade , Manejo da Dor/métodos , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
We report on the immunogenicity and clinical effects in a phase I/II dose escalation trial of a DNA fusion vaccine in patients with prostate cancer. The vaccine encodes a domain (DOM) from fragment C of tetanus toxin linked to an HLA-A2-binding epitope from prostate-specific membrane antigen (PSMA), PSMA(27-35). We evaluated the effect of intramuscular vaccination without or with electroporation (EP) on vaccine potency. Thirty-two HLA-A2(+) patients were vaccinated and monitored for immune and clinical responses for a follow-up period of 72 weeks. At week 24, cross-over to the immunologically more effective delivery modality was permitted; this was shown to be with EP based on early antibody data, and subsequently, 13/15 patients crossed to the +EP arm. Thirty-two HLA-A2(-) control patients were assessed for time to next treatment and overall survival. Vaccination was safe and well tolerated. The vaccine induced DOM-specific CD4(+) and PSMA(27)-specific CD8(+) T cells, which were detectable at significant levels above baseline at the end of the study (p = 0.0223 and p = 0.00248, respectively). Of 30 patients, 29 had a measurable CD4(+) T-cell response and PSMA(27)-specific CD8(+) T cells were detected in 16/30 patients, with or without EP. At week 24, before cross-over, both delivery methods led to increased CD4(+) and CD8(+) vaccine-specific T cells with a trend to a greater effect with EP. PSA doubling time increased significantly from 11.97 months pre-treatment to 16.82 months over the 72-week follow-up (p = 0.0417), with no clear differential effect of EP. The high frequency of immunological responses to DOM-PSMA(27) vaccination and the clinical effects are sufficiently promising to warrant further, randomized testing.
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Antígenos de Superfície/uso terapêutico , Linfócitos T CD8-Positivos/imunologia , Vacinas Anticâncer/administração & dosagem , Glutamato Carboxipeptidase II/uso terapêutico , Ativação Linfocitária/imunologia , Fragmentos de Peptídeos/uso terapêutico , Neoplasias da Próstata/terapia , Toxina Tetânica/uso terapêutico , Vacinas de DNA/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Fusão Gênica Artificial , Linfócitos T CD4-Positivos , Vacinas Anticâncer/imunologia , Eletroporação , Antígeno HLA-A2/análise , Humanos , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/mortalidade , Vacinas de DNA/imunologiaRESUMO
Blast injuries related to explosions have been described in the literature but are uncommon in children. We describe a multisystem blast injury in a child resulting from a commercial firework-related explosion in her home. She presented with respiratory failure, shock, altered level of consciousness, and multiple orthopedic injuries. The patient required immediate stabilization and resuscitation in the emergency department and a prolonged hospitalization. This report reviews the spectrum of injuries that are seen in blast-related trauma and the emergency measures needed for rapid stabilization of these critical patients.
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Acidentes Domésticos , Traumatismos por Explosões/etiologia , Lesão Pulmonar/etiologia , Traumatismo Múltiplo/etiologia , Jogos e Brinquedos , Amputação Traumática/etiologia , Braço , Traumatismos por Explosões/diagnóstico , Traumatismos por Explosões/terapia , Criança , Emergências , Feminino , Fraturas do Fêmur/etiologia , Dedos , Corpos Estranhos/etiologia , Humanos , Lesão Pulmonar/diagnóstico , Lesão Pulmonar/terapia , Traumatismo Múltiplo/diagnóstico , Traumatismo Múltiplo/terapiaRESUMO
In many animals, sperm competition and sexual conflict are thought to drive the rapid evolution of male-specific genes, especially those expressed in the testes. A potential exception occurs in the male pregnant pipefishes, where females transfer eggs to the males, eliminating testes from participating in these processes. Here, we show that testis-related genes differ dramatically in their rates of molecular evolution and expression patterns in pipefishes and seahorses (Syngnathidae) compared to other fish. Genes involved in testis or sperm function within syngnathids experience weaker selection in comparison to their orthologs in spawning and livebearing fishes. An assessment of gene turnover and expression in the testis transcriptome suggests that syngnathids have lost (or significantly reduced expression of) important classes of genes from their testis transcriptomes compared to other fish. Our results indicate that more than 50 million years of male pregnancy have removed syngnathid testes from the molecular arms race that drives the rapid evolution of male reproductive genes in other taxa.
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Smegmamorpha , Animais , Feminino , Peixes/genética , Masculino , Sêmen , Smegmamorpha/genética , Testículo , TranscriptomaRESUMO
The incidence of renal stones in adults has increased significantly over time. Although published evidence is somewhat limited, during the last 10 years, there have been reports of 4-fold increase in the number of children evaluated for nephrolithiasis, and of those, a 7-fold increase in diagnosis of stone disease. The etiology of stone formation has shifted over time, with a transition from infectious causes to metabolic causes. It was our goal in this review of the literature on pediatric renal stone disease to further highlight the changing epidemiology and etiology as well as provide a framework for appropriate clinical evaluation and use of diagnostic tools when approaching a patient with suspected renal stone disease. We also provide guidance regarding treatment and prevention of renal stone disease in children.