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BACKGROUND: OCTOVA compared the efficacy of olaparib (O) versus weekly paclitaxel (wP) or olaparib + cediranib (O + C) in recurrent ovarian cancer (OC). AIMS: The main aim of the OCTOVA trial was to determine the progression-free survival (PFS) of olaparib (O) versus the oral combination of olaparib plus cediranib (O + C) and weekly paclitaxel (wP) in recurrent ovarian cancer (OC). METHODS: In total, 139 participants who had relapsed within 12 months of platinum therapy were randomised to O (300 mg twice daily), wP (80 mg/m2 d1,8,15, q28) or O + C (300 mg twice daily/20 mg daily, respectively). The primary endpoint was progression-free survival (PFS) of olaparib (O) versus olaparib plus cediranib (O + C) or weekly paclitaxel (wP). The sample size was calculated to observe a PFS hazard ratio (HR) 0.64 in favour of O + C compared to O (20% one-sided type I error, 80% power). RESULTS: The majority had platinum-resistant disease (90%), 22% prior PARPi, 34% prior anti-angiogenic therapy, 30% germline BRCA1/2 mutations. The PFS was increased for O + C vs O (O + C 5.4 mo (2.3, 9.6): O 3.7 mo (1.8, 7.6) HR = 0.73; 60% CI: 0.59, 0.89; P = 0.1) and no different between wP and O (wP 3.9 m (1.9, 9.1); O 3.7 mo (1.8, 7.6) HR = 0.89, 60% CI: 0.72, 1.09; P = 0.69). The main treatment-related adverse events included manageable diarrhoea (4% Grade 3) and hypertension (4% Grade 3) in the O + C arm. DISCUSSION: OCTOVA demonstrated the activity of O + C in women with recurrent disease, offering a potential non-chemotherapy option. TRIAL REGISTRATION: ISRCTN14784018, registered on 19th January 2018 http://www.isrctn.com/ISRCTN14784018 .
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Indóis , Neoplasias Ovarianas , Piperazinas , Quinazolinas , Humanos , Feminino , Neoplasias Ovarianas/genética , Proteína BRCA1/genética , Proteína BRCA2/genética , Recidiva Local de Neoplasia/genética , Carcinoma Epitelial do Ovário/tratamento farmacológico , Ftalazinas/efeitos adversos , Paclitaxel/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
We used results from an optimization randomized controlled trial which tested five behavioral intervention components to support HIV antiretroviral adherence/HIV viral suppression, grounded in the multiphase optimization strategy and using a fractional factorial design to identify intervention components with cost-effectiveness sufficiently favorable for scalability. Results were incorporated into a validated HIV computer simulation to simulate longer-term effects of combinations of components on health and costs. We simulated the 32 corresponding long-term trajectories for viral load suppression, health related quality of life (HRQoL), and costs. The components were designed to be culturally and structurally salient. They were: motivational interviewing counseling sessions (MI), pre-adherence skill building (SB), peer mentorship (PM), focused support groups (SG), and patient navigation (short version [NS], long version [NL]. All participants also received health education on HIV treatment. We examined four scenarios: one-time intervention with and without discounting and continuous interventions with and without discounting. In all four scenarios, interventions that comprise or include SB and NL (and including health education) were cost effective (< $100,000/quality-adjusted life year). Further, with consideration of HRQoL impact, maximal intervention became cost-effective enough to be scalable. Thus, a fractional factorial experiment coupled with cost-effectiveness analysis is a promising approach to optimize multi-component interventions for scalability. The present study can guide service planning efforts for HIV care settings and health departments.
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Negro ou Afro-Americano , Análise Custo-Benefício , Infecções por HIV , Hispânico ou Latino , Adesão à Medicação , Entrevista Motivacional , Qualidade de Vida , Carga Viral , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/economia , Terapia Comportamental/métodos , Terapia Comportamental/economia , Negro ou Afro-Americano/psicologia , Aconselhamento/métodos , Aconselhamento/economia , Hispânico ou Latino/psicologia , Hispânico ou Latino/estatística & dados numéricos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/psicologia , Entrevista Motivacional/métodos , Navegação de Pacientes , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
OBJECTIVE: Few individuals with eating disorders (EDs) receive treatment. Innovations are needed to identify individuals with EDs and address care barriers. We developed a chatbot for promoting services uptake that could be paired with online screening. However, it is not yet known which components drive effects. This study estimated individual and combined contributions of four chatbot components on mental health services use (primary), chatbot helpfulness, and attitudes toward changing eating/shape/weight concerns ("change attitudes," with higher scores indicating greater importance/readiness). METHODS: Two hundred five individuals screening with an ED but not in treatment were randomized in an optimization randomized controlled trial to receive up to four chatbot components: psychoeducation, motivational interviewing, personalized service recommendations, and repeated administration (follow-up check-ins/reminders). Assessments were at baseline and 2, 6, and 14 weeks. RESULTS: Participants who received repeated administration were more likely to report mental health services use, with no significant effects of other components on services use. Repeated administration slowed the decline in change attitudes participants experienced over time. Participants who received motivational interviewing found the chatbot more helpful, but this component was also associated with larger declines in change attitudes. Participants who received personalized recommendations found the chatbot more helpful, and receiving this component on its own was associated with the most favorable change attitude time trend. Psychoeducation showed no effects. DISCUSSION: Results indicated important effects of components on outcomes; findings will be used to finalize decision making about the optimized intervention package. The chatbot shows high potential for addressing the treatment gap for EDs.
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To build a coherent knowledge base about what psychological intervention strategies work, develop interventions that have positive societal impact, and maintain and increase this impact over time, it is necessary to replace the classical treatment package research paradigm. The multiphase optimization strategy (MOST) is an alternative paradigm that integrates ideas from behavioral science, engineering, implementation science, economics, and decision science. MOST enables optimization of interventions to strategically balance effectiveness, affordability, scalability, and efficiency. In this review we provide an overview of MOST, discuss several experimental designs that can be used in intervention optimization, consider how the investigator can use experimental results to select components for inclusion in the optimized intervention, discuss the application of MOST in implementation science, and list future issues in this rapidly evolving field. We highlight the feasibility of adopting this new research paradigm as well as its potential to hasten the progress of psychological intervention science.
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Psicologia Clínica , Humanos , Psicologia Clínica/métodos , Intervenção Psicossocial/métodos , Ciência da Implementação , Psicoterapia/métodos , Projetos de PesquisaRESUMO
Interventions (including behavioral, biobehavioral, biomedical, and social-structural interventions) hold tremendous potential not only to improve public health overall but also to reduce health disparities and promote health equity. In this study, we introduce one way in which interventions can be optimized for health equity in a principled fashion using the multiphase optimization strategy (MOST). Specifically, we define intervention equitability as the extent to which the health benefits provided by an intervention are distributed evenly versus concentrated among those who are already advantaged, and we suggest that, if intervention equitability is acknowledged to be a priority, then equitability should be a key criterion that is balanced with other criteria (effectiveness overall, as well as affordability, scalability, and/or efficiency) in intervention optimization. Using a hypothetical case study and simulated data, we show how MOST can be applied to achieve a strategic balance that incorporates equitability. We also show how the composition of an optimized intervention can differ when equitability is considered versus when it is not. We conclude with a vision for next steps to build on this initial foray into optimizing interventions for equitability.
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Equidade em Saúde , Humanos , Promoção da SaúdeRESUMO
BACKGROUND: The dense stroma of pancreatic ductal adenocarcinomas is a major barrier to drug delivery. To increase the local drug diffusion gradient, high doses of chemotherapeutic agent doxorubicin can be released from thermally-sensitive liposomes (ThermoDox®) using ultrasound-mediated hyperthermia at the tumour target. PanDox is designed as a Phase 1 single centre study to investigate enhancing drug delivery to adult patients with non-operable pancreatic ductal adenocarcinomas. The study compares a single cycle of either conventional doxorubicin alone or ThermoDox® with focused ultrasound-induced hyperthermia for targeted drug release. METHODS: Adults with non-resectable pancreatic ductal adenocarcinoma are allocated to receive a single cycle of either doxorubicin alone (Arm A) or ThermoDox® with focused ultrasound-induced hyperthermia (Arm B), based on patient- and tumour-specific safety conditions. Participants in Arm B will undergo a general anaesthetic and pre-heating of the tumour by extra-corporal focused ultrasound (FUS). Rather than employing invasive thermometry, ultrasound parameters are derived from a patient-specific treatment planning model to reach the 41 °C target temperature for drug release. ThermoDox® is then concurrently infused with further ultrasound exposure. Tumour biopsies at the targeted site from all patients are analysed post-treatment using high performance liquid chromatography to quantify doxorubicin delivered to the tumour. The primary endpoint is defined as a statistically significant enhancement in concentration of total intra-tumoural doxorubicin, comparing samples from patients receiving liposomal drug with FUS to free drug alone. Participants are followed for 21 days post-treatment to assess secondary endpoints, including radiological assessment to measure changes in tumour activity by Positron Emission Tomography Response Criteria in Solid Tumours (PERCIST) criteria, adverse events and patient-reported symptoms. DISCUSSION: This early phase study builds on previous work targeting tumours in the liver to investigate whether enhancement of chemotherapy delivery using ultrasound-mediated hyperthermia can be translated to the stroma-dense environment of pancreatic ductal adenocarcinoma. If successful, it could herald a new approach towards managing these difficult-to-treat tumours. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04852367 . Registered 21st April 2022. EudraCT number: 2019-003950-10 (Registered 2019) Iras Project ID: 272253 (Registered 2019) Ethics Number: 20/EE/0284.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Policetídeos , Adulto , Humanos , Tomografia Computadorizada por Raios X , Doxorrubicina/uso terapêutico , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/tratamento farmacológico , Antraciclinas , Antibióticos Antineoplásicos/uso terapêutico , Carcinoma Ductal Pancreático/diagnóstico por imagem , Carcinoma Ductal Pancreático/tratamento farmacológico , Ensaios Clínicos Fase I como Assunto , Neoplasias PancreáticasRESUMO
There is an urgent need for efficient behavioral interventions to increase rates of HIV viral suppression for populations with serious barriers to engagement along the HIV care continuum. We carried out an optimization trial to test the effects of five behavioral intervention components designed to address barriers to HIV care continuum engagement for African American/Black and Latino persons living with HIV (PLWH) with non-suppressed HIV viral load levels: motivational interviewing sessions (MI), focused support groups (SG), peer mentorship (PM), pre-adherence skill building (SB), and navigation with two levels, short (NS) and long (NL). The primary outcome was HIV viral suppression (VS) and absolute viral load (VL) and health-related quality of life were secondary outcomes. Participants were 512 African American/Black and Latino PLWH poorly engaged in HIV care and with detectable HIV viral load levels in New York City, recruited mainly through peer referral. Overall, VS increased to 37%, or 45% in a sensitivity analysis. MI and SG seemed to have antagonistic effects on VS (z = - 1.90; p = 0.057); the probability of VS was highest when either MI or SG was assigned, but not both. MI (Mean Difference = 0.030; 95% CI 0.007-0.053; t(440) = 2.60; p = 0.010) and SB (Mean Difference = 0.030; 95% CI 0.007-0.053; t(439) = 2.54; p = 0.012) improved health-related quality of life. This is the first optimization trial in the field of HIV treatment. The study yields a number of insights into approaches to improve HIV viral suppression in PLWH with serious barriers to engagement along the HIV care continuum, including chronic poverty, and underscores challenges inherent in doing so.
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Negro ou Afro-Americano , Infecções por HIV , Humanos , Hispânico ou Latino , Infecções por HIV/terapia , Qualidade de Vida , Carga ViralRESUMO
STUDY OBJECTIVE: Tobacco dependence treatment initiated in the hospital emergency department (ED) is effective. However, trials typically use multicomponent interventions, making it difficult to distinguish specific components that are effective. In addition, interactions between components cannot be assessed. The Multiphase Optimization Strategy allows investigators to identify these effects. METHODS: We conducted a full-factorial, 24 or 16-condition optimization trial in a busy hospital ED to examine the performance of 4 tobacco dependence interventions: a brief negotiation interview; 6 weeks of nicotine replacement therapy with the first dose delivered in the ED; active referral to a telephone quitline; and enrollment in SmokefreeTXT, a free short-messaging service program. Study data were analyzed with a novel mixed methods approach to assess clinical efficacy, cost-effectiveness, and qualitative participant feedback. The primary endpoint was tobacco abstinence at 3 months, verified by exhaled carbon monoxide using a Bedfont Micro+ Smokerlyzer. RESULTS: Between February 2017 and May 2019, we enrolled 1,056 adult smokers visiting the ED. Odd ratios (95% confidence intervals) from the primary analysis of biochemically confirmed abstinence rates at 3 months for each intervention, versus control, were: brief negotiation interview, 1.8 (1.1, 2.8); nicotine replacement therapy, 2.1 (1.3, 3.2); quitline, 1.4 (0.9, 2.2); SmokefreeTXT, 1.1 (0.7, 1.7). There were no statistically significant interactions among components. Economic and qualitative analyses are in progress. CONCLUSION: The brief negotiation interview and nicotine replacement therapy were efficacious. This study is the first to identify components of ED-initiated tobacco dependence treatment that are individually effective. Future work will address the scalability of the brief negotiation interview and nicotine replacement therapy by offering provider-delivered brief negotiation interviews and nicotine replacement therapy prescriptions.
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Alcoolismo , Abandono do Hábito de Fumar , Tabagismo , Adulto , Humanos , Tabagismo/terapia , Abandono do Hábito de Fumar/métodos , Dispositivos para o Abandono do Uso de Tabaco , Resultado do Tratamento , Serviço Hospitalar de EmergênciaRESUMO
BACKGROUND: The persistence of racial/ethnic inequities in rates of engagement along the HIV care continuum signals the need for novel approaches. We developed six behavioral intervention components for use in an optimization trial, grounded in a model that integrates critical race theory, harm reduction, and self-determination theory, designed to address various barriers that African American/Black and Latino persons living with HIV (PLWH) experience to the HIV care continuum. The components were: health education, motivational interviewing sessions, pre-adherence skill building, peer mentorship, focused support groups, and navigation. The present qualitative exploratory study describes participants' perspectives on the components' acceptability, feasibility, and impact. METHODS: Participants were African American/Black and Latino PLWH poorly engaged in HIV care and with non-suppressed HIV viral load in New York City. From a larger trial, we randomly selected 46 participants for in-depth semi-structured interviews. Interviews were audio-recorded and transcribed verbatim, and data were analyzed using directed content analysis. Quantitative data on sociodemographic and background characteristics and components' acceptability and feasibility were also collected. RESULTS: On average, participants were 49 years old and had lived with HIV for 19 years. Most were cisgender-male and African American/Black. Participants reported a constellation of serious social and structural challenges to HIV management including chronic poverty, unstable housing, and stigma. Across components, a non-judgmental and pressure-free approach and attention to structural and cultural factors were seen as vital to high levels of engagement, but lacking in most medical/social service settings. Prominent aspects of individual components included establishing trust (health education); developing intrinsic motivation, goals, and self-reflection (motivational interviewing sessions); learning/practicing adherence strategies and habits (pre-adherence skill building); reducing social isolation via peer role models (peer mentorship); reflecting on salient goals and common challenges with peers without stigma (focused support groups); and circumventing structural barriers to HIV management with support (navigation). Components were found acceptable and feasible. Findings suggested ways components could be improved. CONCLUSIONS: The present study advances research on interventions for African American/Black and Latino PLWH, who experience complex barriers to engagement along the HIV care continuum. Future study of the components is warranted to address racial/ethnic health inequities in HIV.
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Negro ou Afro-Americano , Infecções por HIV , Humanos , Masculino , Estados Unidos , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde , Carga Viral , Hispânico ou Latino , Infecções por HIV/terapiaRESUMO
BACKGROUND: The benefits of moderate to vigorous physical activity (MVPA) for breast cancer survivors are well established. However, most are insufficiently active. Fit2Thrive used the Multiphase Optimization Strategy methodology to determine the effect of 5 intervention components on MVPA in this population. METHODS: Two hundred sixty-nine participants (mean age, 52.5 years; SD, 9.9 years) received a core intervention (the Fit2Thrive self-monitoring app and Fitbit) and were randomly assigned to 5 intervention components set to on/off in a full factorial experiment: support calls, deluxe app, buddy, online gym, and text messages. The intervention was delivered over 12 weeks with a 12-week follow-up. MVPA was measured via accelerometry at the baseline (T1), at 12 weeks (T2), and at 24 weeks (T3). The main effects and interaction effects at each time point were examined for all components. RESULTS: Trial retention was high: 91.8% had valid accelerometer data at T2 or T3. Across all conditions, there were significant increases in MVPA (+53.6 min/wk; P < .001) and in the proportion of survivors meeting MVPA guidelines (+22.3%; P < .001) at T2 that were maintained but attenuated at T3 (MVPA, +24.6 min/wk; P < .001; meeting guidelines, +12.6%; P < .001). No individual components significantly improved MVPA, although increases were greater for the on level versus the off level for support calls, buddy, and text messages at T2 and T3. CONCLUSIONS: The Fit2Thrive core intervention (the self-monitoring app and Fitbit) is promising for increasing MVPA in breast cancer survivors, but the components provided no additional increases in MVPA. Future research should evaluate the core intervention in a randomized trial and determine what components optimize MVPA behaviors in breast cancer survivors.
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Neoplasias da Mama , Sobreviventes de Câncer , Exercício Físico , Acelerometria , Adulto , Neoplasias da Mama/reabilitação , Feminino , Humanos , Pessoa de Meia-Idade , Aplicativos Móveis , Monitorização Ambulatorial , Autocuidado , TecnologiaRESUMO
BACKGROUND: Rates of participation in HIV care, medication uptake, and viral suppression are improving among persons living with HIV (PLWH) in the United States. Yet, disparities among African American/Black and Latino PLWH are persistent, signaling the need for new conceptual approaches. To address gaps in services and research (e.g., insufficient attention to structural/systemic factors, inadequate harm reduction services and autonomy support) and improve behavioral interventions, we integrated critical race theory, harm reduction, and self-determination theory into a new conceptual model, then used the model to develop a set of six intervention components which were tested in a larger study. The present qualitative study explores participants' perspectives on the study's acceptability, feasibility, and impact, and the conceptual model's contribution to these experiences. METHODS: Participants in the larger study were African American/Black and Latino PLWH poorly engaged in HIV care and with non-suppressed HIV viral load in New York City (N = 512). We randomly selected N = 46 for in-depth semi-structured interviews on their experiences with and perspectives on the study. Interviews were audio-recorded and professionally transcribed verbatim, and data were analyzed using directed qualitative content analysis. RESULTS: On average, participants were 49 years old (SD = 9) and had lived with HIV for 19 years (SD = 7). Most were male (78%) and African American/Black (76%). All had taken HIV medication previously. Challenging life contexts were the norm, including poverty, poor quality/unstable housing, trauma histories exacerbated by current trauma, health comorbidities, and substance use. Participants found the study highly acceptable. We organized results into four themes focused on participants' experiences of: 1) being understood as a whole person and in their structural/systemic context; 2) trustworthiness and trust; 3) opportunities for self-reflection; and 4) support of personal autonomy. The salience of nonjudgment was prominent in each theme. Themes reflected grounding in the conceptual model. Participants reported these characteristics were lacking in HIV care settings. CONCLUSIONS: The new conceptual model emphasizes the salience of systemic/structural and social factors that drive health behavior and the resultant interventions foster trust, self-reflection, engagement, and behavior change. The model has potential to enhance intervention acceptability, feasibility, and effectiveness with African American/Black and Latino PLWH.
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Negro ou Afro-Americano , Infecções por HIV , Feminino , Infecções por HIV/tratamento farmacológico , Redução do Dano , Hispânico ou Latino , Humanos , Masculino , Pessoa de Meia-Idade , Autonomia Pessoal , Estados UnidosRESUMO
The classical two-arm randomized clinical trial (RCT) is designed to test the efficacy or effectiveness of an intervention, which may consist of one or more components. However, this approach does not enable the investigator to obtain information that is important in intervention development, such as which individual components of the intervention are efficacious, which are not and possibly should be removed, and whether any components interact. The Multiphase Optimization Strategy (MOST) is a new framework for development, optimization, and evaluation of interventions. MOST includes the RCT for purposes of evaluation, but inserts a phase of research before the RCT aimed at intervention optimization. The optimization phase requires one or more separate trials similar in scope to an RCT, but employing a different experimental design. The design of the optimization trial is selected strategically so as to maximize the amount of scientific information gained using the available resources. One consideration in selecting this experimental design is the type of intervention to be optimized. If a fixed intervention, i.e. one in which the same intervention content and intensity is provided to all participants, is to be optimized, a factorial experiment is often appropriate. If an adaptive intervention, i.e. one in which intervention content or intensity is varied in a principled manner, is to be optimized, a sequential multiple-assignment randomized trial (SMART) is often a good choice. The objective of this article is to describe MOST and the scientific rationale for its use; describe two current applications of MOST in emergency medicine research, one using a factorial experiment and the other using a SMART; and discuss funding strategies and potential future applications in studying the care of individuals with acute illness, injury, or behavioral disorders.
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Medicina de Emergência , Projetos de Pesquisa , Humanos , Cuidados Paliativos , PesquisadoresRESUMO
BACKGROUND: Using the multiphase optimization strategy (MOST), we previously developed and optimized an online behavioral intervention, itMatters, aimed at reducing the risk of sexually transmitted infections (STI) among first-year college students by targeting the intersection of alcohol use and sexual behaviors. PURPOSE: We had two goals: (a) to evaluate the optimized itMatters intervention and (b) to determine whether the candidate sexual violence prevention (SVP) component (included at the request of participating universities) had a detectable effect and therefore should be added to create a new version of itMatters. We also describe the hybrid evaluation-optimization trial we conducted to accomplish these two goals in a single experiment. METHODS: First year college students (N = 3,098) at four universities in the USA were individually randomized in a hybrid evaluation-optimization 2 × 2 factorial trial. Data were analyzed using regression models, with pre-test outcome variables included as covariates in the models. Analyses were conducted separately with (a) immediate post-test scores and (b) 60-day follow-up scores as outcome variables. RESULTS: Experimental results indicated a significant effect of itMatters on targeted proximal outcomes (norms) and on one distal behavioral outcome (binge drinking). There were no significant effects on other behavioral outcomes, including the intersection of alcohol and sexual behaviors. In addition, there were mixed results (positive short-term effect; no effect at 60-day follow-up) of the SVP component on targeted proximal outcomes (students' self-efficacy to reduce/prevent sexual violence and perceived effectiveness of protective behavioral strategies). CONCLUSIONS: The hybrid evaluation-optimization trial enabled us to evaluate the individual and combined effectiveness of the optimized itMatters intervention and the SVP component in a single experiment, conserving resources and providing greatly improved efficiency. TRIAL REGISTRATION: NCT04095065.
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Delitos Sexuais , Estudantes , Consumo de Bebidas Alcoólicas/prevenção & controle , Humanos , Delitos Sexuais/prevenção & controle , Comportamento Sexual , UniversidadesRESUMO
Substance use problems are highly prevalent among persons living with (PLWH) in the United States and serve as serious barriers to engagement in HIV care. Yet, in contrast to studies of single substances, little is known about patterns of polysubstance use in this population. Moreover, other risk factors (e.g., financial hardship, incarceration, homelessness, and mental health distress) are also prevalent and complicate HIV management. The present study drew on a cross-sectional survey with African American/Black and Latino (AABL) adult PLWH from low socioeconomic status backgrounds in New York City who were insufficiently engaged in HIV care and evidenced detectable HIV viral load (N = 512). We used latent class analysis (LCA) to explore patterns of polysubstance use and their relationships to financial hardship, incarceration, homelessness, and mental health. LCA yielded three substance use classes: Class 1, a high polysubstance use/high-risk substance use class (9%); Class 2, a polysubstance use/moderate substance use risk class (18%); and Class 3, a moderate polysubstance use/moderate-to-low-risk substance use class (74%). Mental health symptoms were prevalent in all classes, but Class 1 had greater mental health distress than the other two classes. Current homelessness was more prevalent in Classes 1 and 2. We cannot end the HIV epidemic without engaging and treating AABL PLWH who have serious barriers to engagement along the HIV care continuum, and who evidence polysubstance use along with co-occurring risk factors. Clinical settings can develop outreach and engagement approaches to bring this subpopulation of PLWH into care settings, and further, specialized services are needed to successfully screen, treat, and retain them.
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Infecções por HIV , Transtornos Relacionados ao Uso de Substâncias , Adulto , Negro ou Afro-Americano , Estudos Transversais , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Hispânico ou Latino , Humanos , Análise de Classes Latentes , Cidade de Nova Iorque/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/complicações , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Estados Unidos/epidemiologia , Carga ViralRESUMO
The COVID-19 pandemic has great potential to disrupt the lives of persons living with HIV (PLWH). The present convergent parallel design mixed-methods study explored the early effects of COVID-19 on African American/Black or Latino (AABL) long-term survivors of HIV in a pandemic epicenter, New York City. A total of 96 AABL PLWH were recruited from a larger study of PLWH with non-suppressed HIV viral load. They engaged in structured assessments focused on knowledge, testing, trust in information sources, and potential emotional, social, and behavioral impacts. Twenty-six of these participants were randomly selected for in-depth semi-structured interviews. Participants were mostly men (64%), African American/Black (75%), and had lived with HIV for 17 years, on average (SD=9 years). Quantitative results revealed high levels of concern about and the adoption of recommended COVID-19 prevention recommendations. HIV care visits were commonly canceled but, overall, engagement in HIV care and antiretroviral therapy use were not seriously disrupted. Trust in local sources of information was higher than trust in various federal sources. Qualitative findings complemented and enriched quantitative results and provided a multifaceted description of both risk factors (e.g., phones/internet access were inadequate for some forms of telehealth) and resilience (e.g., "hustling" for food supplies). Participants drew a direct line between structural racism and the disproportional adverse effects of COVID-19 on communities of color, and their knowledge gleaned from the HIV pandemic was applied to COVID-19. Implications for future crisis preparedness are provided, including how the National HIV/AIDS Strategy can serve as a model to prevent COVID-19 from becoming another pandemic of the poor.
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COVID-19 , Infecções por HIV , Negro ou Afro-Americano , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Hispânico ou Latino , Humanos , Masculino , Cidade de Nova Iorque/epidemiologia , Pandemias/prevenção & controle , SARS-CoV-2RESUMO
BACKGROUND: Although periods of HIV antiretroviral therapy (ART) discontinuation have deleterious health effects, ART is not always sustained. Yet, little is known about factors that contribute to such ART non-persistence among long-term HIV survivors. The present study applied a convergent parallel mixed-methods design to explore the phenomena of stopping/starting and sustaining ART, focusing on low-socioeconomic status African American or Black and Latino persons living with HIV (PLWH) who face the greatest challenges. METHODS: Participants (N = 512) had poor engagement in HIV care and detectable HIV viral load. All received structured assessments and N = 48 were randomly selected for in-depth interviews. Quantitative analysis using negative binomial regression uncovered associations among multi-level factors and the number of times ART was stopped/started and the longest duration of sustained ART. Qualitative data were analyzed using a directed content analysis approach and results were integrated. RESULTS: Participants were diagnosed 18.2 years ago on average (SD = 8.6), started ART a median five times (Q1 = 3, Q3 = 10), and the median longest duration of sustained ART was 18 months (Q1 = 6, Q3 = 36). Factors associated with higher rates of stops/starts were male sex, transgender identity, cannabis use at moderate-to-high-risk levels, and ART- and care-related stigma. Factors associated with lower rates of stops/starts were older age, more years since diagnosis, motivation for care, and lifetime injection drug use (IDU). Factors associated with longer durations of sustained ART were Latino/Hispanic ethnicity, motivation for ART and care, and recent IDU. Factors associated with a shorter duration were African American/Black race, alcohol use at moderate-to-high-risk levels, and social support. Qualitative results uncovered a convergence of intersecting risk factors for stopping/starting ART and challenges inherent in managing HIV over decades in the context of poverty. These included unstable housing, which contributed to social isolation, mental health distress, and substance use concerns, the latter prompting selling ("diverting") ART. Primarily complementary quantitative and qualitative findings described mechanisms by which risk/protective factors operated and ways PLWH successfully restart and/or sustain ART. CONCLUSIONS: The field focuses substantially on ART adherence, but greater attention to reducing the frequency of ART non-persistence is needed, along with creating social/structural conditions favorable for sustained ART.
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Negro ou Afro-Americano , Infecções por HIV , Idoso , Antirretrovirais/uso terapêutico , Feminino , Infecções por HIV/tratamento farmacológico , Hispânico ou Latino , Humanos , Masculino , SobreviventesRESUMO
Wayne Velicer is remembered for a mind where mathematical concepts and calculations intrigued him, behavioral science beckoned him, and people fascinated him. Born in Green Bay, Wisconsin on March 4, 1944, he was raised on a farm, although early influences extended far beyond that beginning. His Mathematics BS and Psychology minor at Wisconsin State University in Oshkosh, and his PhD in Quantitative Psychology from Purdue led him to a fruitful and far-reaching career. He was honored several times as a high-impact author, was a renowned scholar in quantitative and health psychology, and had more than 300 scholarly publications and 54,000+ citations of his work, advancing the arenas of quantitative methodology and behavioral health. In his methodological work, Velicer sought out ways to measure, synthesize, categorize, and assess people and constructs across behaviors and time, largely through principal components analysis, time series, and cluster analysis. Further, he and several colleagues developed a method called Testing Theory-based Quantitative Predictions, successfully applied to predicting outcomes and effect sizes in smoking cessation, diet behavior, and sun protection, with the potential for wider applications. With $60,000,000 in external funding, Velicer also helped engage a large cadre of students and other colleagues to study methodological models for a myriad of health behaviors in a widely applied Transtheoretical Model of Change. Unwittingly, he has engendered indelible memories and gratitude to all who crossed his path. Although Wayne Velicer left this world on October 15, 2017 after battling an aggressive cancer, he is still very present among us.
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Medicina do Comportamento , Tutoria , HumanosRESUMO
BACKGROUND: Aiming to improve treatment options for BRAF wild-type melanoma, we previously conducted the DOC-MEK study of docetaxel with MEK inhibitor (MEKi) selumetinib or placebo, revealing trends to prolongation of progression-free survival (hazard ratio 0.75, P = 0.130), and improved response rates (32% vs 14%, P = 0.059) with docetaxel plus selumetinib. NRAS status did not associate with outcome. Here, the aim was to identify novel biomarkers of response to MEKi. METHODS: A MEK 6 gene signature was quantified using NanoString and correlated with clinical outcomes. Two components of the gene signature were investigated by gene silencing in BRAF/NRAS wild-type melanoma cells. RESULTS: In melanomas of patients on the selumetinib but not the placebo arm, two gene signature components, dual-specificity protein phosphatase 4 (DUSP4) and ETS translocation variant 4 (ETV4), were expressed more highly in responders than non-responders. In vitro, ETV4 depletion inhibited cell survival but did not influence sensitivity to MEKi selumetinib or trametinib. In contrast, DUSP4-depleted cells showed enhanced cell survival and increased resistance to both selumetinib and trametinib. CONCLUSIONS: ETV4 and DUSP4 associated with clinical response to docetaxel plus selumetinib. DUSP4 depletion induced MEKi resistance, suggesting that DUSP4 is not only a biomarker but also a mediator of MEKi sensitivity. CLINICAL TRIAL REGISTRATION: DOC-MEK (EudraCT no: 2009-018153-23).
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Fosfatases de Especificidade Dupla/genética , Melanoma/genética , Fosfatases da Proteína Quinase Ativada por Mitógeno/genética , Proteínas Proto-Oncogênicas c-ets/genética , Benzimidazóis/administração & dosagem , Docetaxel/administração & dosagem , Humanos , MAP Quinase Quinase Quinases/antagonistas & inibidores , Melanoma/tratamento farmacológico , Proteínas Proto-Oncogênicas B-raf/genética , TranscriptomaRESUMO
BACKGROUND: The Multiphase Optimization Strategy (MOST) is an approach to systematically and efficiently developing a behavioral intervention using a sequence of experiments to prepare and optimize the intervention. PURPOSE: Using a 6 year MOST-based behavioral intervention development project as an example, we outline the results-and resulting decision-making process-related to experiments at each step to display the practical challenges present at each stage. METHODS: To develop a positive psychology (PP) based intervention to promote physical activity after an acute coronary syndrome (N = 255 across four phases), we utilized qualitative, proof-of-concept, factorial design, and randomized pilot experiments, with iterative modification of intervention content and delivery. RESULTS: Through this multiphase approach, we ultimately developed a 12 week, phone-delivered, combined PP-motivational interviewing intervention to promote physical activity. Across stages, we learned several important lessons: (a) participant and interventionist feedback is important, even in later optimization stages; (b) a thoughtful and systematic approach using all information sources is required when conflicting results in experiments make next steps unclear; and (3) new approaches in the field over a multiyear project should be integrated into the development process. CONCLUSIONS: A MOST-based behavioral intervention development program can be efficient and effective in developing optimized new interventions, and it may require complex and nuanced decision-making at each phase.
Assuntos
Síndrome Coronariana Aguda/reabilitação , Exercício Físico , Entrevista Motivacional , Avaliação de Processos e Resultados em Cuidados de Saúde , Psicologia Positiva , Intervenção Psicossocial , Estudos de Viabilidade , Humanos , Entrevista Motivacional/métodos , Projetos Piloto , Estudo de Prova de Conceito , Psicologia Positiva/métodos , Intervenção Psicossocial/métodos , Pesquisa QualitativaRESUMO
BACKGROUND: Persons living with HIV (PLWH) are living longer, although racial/ethnic and socioeconomic status (SES) disparities persist. Yet, little is known about the experience of living with and managing HIV over decades. The present study took a qualitative approach and used the lens of symbolic violence, a type of internalized, non-physical violence manifested in the power differential between social groups. We focused on adult African American/Black and Latinx (AABL) PLWH from low-SES backgrounds. METHODS: Data were drawn from two studies with AABL PLWH in New York City (N = 59). After providing signed informed consent, participants engaged in in-depth semi-structured interviews on aspects of HIV management. Interviews were audio-recorded and professionally transcribed verbatim, and data were analyzed using directed qualitative content analysis. RESULTS: Participants in the two studies were comparable on sociodemographic and background characteristics. They had lived with HIV for 20 years, on average (range 3-33 years). All were from low-SES backgrounds and most were African American/Black and men. Participants experienced a convergence of multiple social exclusions, harms, and stigmas, consistent with symbolic violence, which contributed to disengagement from HIV care and discontinuation of HIV medications. We organized results into five sub-themes: (1) participants were "ground down" over time by material, social, and emotional challenges and this diminished self-worth and, at times, the will to live; (2) social isolation and self-isolation, based in part on feeling devalued and dehumanized, served as stigma-avoidance strategies and mechanisms of social exclusion; (3) stigmatizing aspects of patient-provider interactions, both experienced and anticipated, along with (4) restricted autonomy in HIV care and other settings (e.g., parole) reduced engagement; and (5) poor HIV management was internalized as a personal failure. Importantly, resilience was evident throughout the five sub-themes. CONCLUSIONS: Symbolic violence is a useful framework for understanding long-term HIV management and survivorship among AABL PLWH from low-SES backgrounds. Indeed, forms of symbolic violence are internalized over time (e.g., experiencing devaluation, dehumanization, loss of self-worth, and anticipated stigma), thereby impeding successful HIV management, in part because avoiding HIV care and discontinuing HIV medications are primary coping strategies. Results have implications for interventions in community and health care settings.