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California faces several serious direct and indirect climate exposures that can adversely affect public health, some of which are already occurring. The public health burden now and in the future will depend on atmospheric greenhouse gas concentrations, underlying population vulnerabilities, and adaptation efforts. Here, we present a structured review of recent literature to examine the leading climate risks to public health in California, including extreme heat, extreme precipitation, wildfires, air pollution, and infectious diseases. Comparisons among different climate-health pathways are difficult due to inconsistencies in study design regarding spatial and temporal scales and health outcomes examined. We find, however, that the current public health burden likely affects thousands of Californians each year, depending on the exposure pathway and health outcome. Further, while more evidence exists for direct and indirect proximal health effects that are the focus of this review, distal pathways (e.g., impacts of drought on nutrition) are more uncertain but could add to this burden. We find that climate adaptation measures can provide significant health benefits, particularly in disadvantaged communities. We conclude with priority recommendations for future analyses and solution-driven policy actions.
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Mudança Climática , Saúde Pública , Humanos , California , Populações Vulneráveis/estatística & dados numéricos , Poluição do Ar/análise , Poluição do Ar/efeitos adversos , Exposição Ambiental/efeitos adversos , Incêndios FlorestaisRESUMO
Urban environments contribute substantially to the rising burden of cardiometabolic diseases worldwide. Cities are complex adaptive systems that continually exchange resources, shaping exposures relevant to human health such as air pollution, noise, and chemical exposures. In addition, urban infrastructure and provisioning systems influence multiple domains of health risk, including behaviors, psychological stress, pollution, and nutrition through various pathways (eg, physical inactivity, air pollution, noise, heat stress, food systems, the availability of green space, and contaminant exposures). Beyond cardiometabolic health, city design may also affect climate change through energy and material consumption that share many of the same drivers with cardiometabolic diseases. Integrated spatial planning focusing on developing sustainable compact cities could simultaneously create heart-healthy and environmentally healthy city designs. This article reviews current evidence on the associations between the urban exposome (totality of exposures a person experiences, including environmental, occupational, lifestyle, social, and psychological factors) and cardiometabolic diseases within a systems science framework, and examines urban planning principles (eg, connectivity, density, diversity of land use, destination accessibility, and distance to transit). We highlight critical knowledge gaps regarding built-environment feature thresholds for optimizing cardiometabolic health outcomes. Last, we discuss emerging models and metrics to align urban development with the dual goals of mitigating cardiometabolic diseases while reducing climate change through cross-sector collaboration, governance, and community engagement. This review demonstrates that cities represent crucial settings for implementing policies and interventions to simultaneously tackle the global epidemics of cardiovascular disease and climate change.
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Poluição do Ar , Saúde da População Urbana , Humanos , Cidades/epidemiologia , Poluição do Ar/efeitos adversosRESUMO
BACKGROUND: Results from the COORDINATE-Diabetes trial (Coordinating Cardiology Clinics Randomized Trial of Interventions to Improve Outcomes - Diabetes) demonstrated that a multifaceted, clinic-based intervention increased prescription of evidence-based medical therapies to participants with type 2 diabetes and atherosclerotic cardiovascular disease. This secondary analysis assessed whether intervention success was consistent across sex, race, and ethnicity. METHODS: COORDINATE-Diabetes, a cluster randomized trial, recruited participants from 43 US cardiology clinics (20 randomized to intervention and 23 randomized to usual care). The primary outcome was the proportion of participants prescribed all 3 groups of evidence-based therapy (high-intensity statin, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, and sodium-glucose cotransporter-2 inhibitor or glucagon-like peptide 1 receptor agonist) at last trial assessment (6 to 12 months). In this prespecified analysis, mixed-effects logistic regression models were used to assess the outcome by self-reported sex, race, and ethnicity in the intervention and usual care groups, with adjustment for baseline characteristics, medications, comorbidities, and site location. RESULTS: Among 1045 participants with type 2 diabetes and atherosclerotic cardiovascular disease, the median age was 70 years, 32% were female, 16% were Black, and 9% were Hispanic. At the last trial assessment, there was an absolute increase in the proportion of participants prescribed all 3 groups of evidence-based therapy in women (36% versus 15%), Black participants (41% versus 18%), and Hispanic participants (46% versus 18%) with the intervention compared with usual care, with consistent benefit across sex (male versus female; Pinteraction=0.44), race (Black versus White; Pinteraction=0.59), and ethnicity (Hispanic versus Non-Hispanic; Pinteraction= 0.78). CONCLUSIONS: The COORDINATE-Diabetes intervention successfully improved delivery of evidence-based care, regardless of sex, race, or ethnicity. Widespread dissemination of this intervention could improve equitable health care quality, particularly among women and minority communities who are frequently underrepresented in clinical trials. REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03936660.
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Diabetes Mellitus Tipo 2 , Humanos , Feminino , Masculino , Diabetes Mellitus Tipo 2/etnologia , Diabetes Mellitus Tipo 2/terapia , Idoso , Pessoa de Meia-Idade , Doenças Cardiovasculares/etnologia , Fatores Sexuais , Etnicidade , Medicina Baseada em Evidências , Resultado do Tratamento , Estados Unidos/epidemiologia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêuticoRESUMO
BACKGROUND: While it has been hypothesized that high plaque stress and strain may be related to plaque rupture, its direct verification using in vivo coronary plaque rupture data and full 3-dimensional fluid-structure interaction models is lacking in the current literature due to difficulty in obtaining in vivo plaque rupture imaging data from patients with acute coronary syndrome. This case-control study aims to use high-resolution optical coherence tomography-verified in vivo plaque rupture data and 3-dimensional fluid-structure interaction models to seek direct evidence for the high plaque stress/strain hypothesis. METHODS: In vivo coronary plaque optical coherence tomography data (5 ruptured plaques, 5 no-rupture plaques) were acquired from patients using a protocol approved by the local institutional review board with informed consent obtained. The ruptured caps were reconstructed to their prerupture morphology using neighboring plaque cap and vessel geometries. Optical coherence tomography-based 3-dimensional fluid-structure interaction models were constructed to obtain plaque stress, strain, and flow shear stress data for comparative analysis. The rank-sum test in the nonparametric test was used for statistical analysis. RESULTS: Our results showed that the average maximum cap stress and strain values of ruptured plaques were 142% (457.70 versus 189.22 kPa; P=0.0278) and 48% (0.2267 versus 0.1527 kPa; P=0.0476) higher than that for no-rupture plaques, respectively. The mean values of maximum flow shear stresses for ruptured and no-rupture plaques were 145.02 dyn/cm2 and 81.92 dyn/cm2 (P=0.1111), respectively. However, the flow shear stress difference was not statistically significant. CONCLUSIONS: This preliminary case-control study showed that the ruptured plaque group had higher mean maximum stress and strain values. Due to our small study size, larger scale studies are needed to further validate our findings.
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Doença da Artéria Coronariana , Vasos Coronários , Placa Aterosclerótica , Estresse Mecânico , Tomografia de Coerência Óptica , Humanos , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/fisiopatologia , Vasos Coronários/patologia , Ruptura Espontânea , Estudos de Casos e Controles , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/fisiopatologia , Masculino , Feminino , Pessoa de Meia-Idade , Modelos Cardiovasculares , Idoso , Valor Preditivo dos Testes , Síndrome Coronariana Aguda/diagnóstico por imagem , Síndrome Coronariana Aguda/fisiopatologia , Síndrome Coronariana Aguda/etiologiaRESUMO
High incidences of congenital syphilis have been reported in areas along the Pacific coast of Colombia. In this retrospective study, conducted during 2018-2022 at a public hospital in Buenaventura, Colombia, we analyzed data from 3,378 pregnant women. The opportunity to prevent congenital syphilis was missed in 53.1% of mothers because of the lack of syphilis screening. Characteristics of higher maternal social vulnerability and late access to prenatal care decreased the probability of having >1 syphilis screening test, thereby increasing the probability of having newborns with congenital syphilis. In addition, the opportunity to prevent congenital syphilis was missed in 41.5% of patients with syphilis because of the lack of treatment, which also increased the probability of having newborns with congenital syphilis. We demonstrate the urgent need to improve screening and treatment capabilities for maternal syphilis, particularly among pregnant women who are more socially vulnerable.
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Complicações Infecciosas na Gravidez , Sífilis Congênita , Humanos , Colômbia/epidemiologia , Feminino , Sífilis Congênita/prevenção & controle , Sífilis Congênita/epidemiologia , Gravidez , Estudos Retrospectivos , Adulto , Complicações Infecciosas na Gravidez/prevenção & controle , Complicações Infecciosas na Gravidez/epidemiologia , Recém-Nascido , Adulto Jovem , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Cuidado Pré-Natal , Programas de Rastreamento , Sífilis/epidemiologia , Sífilis/prevenção & controle , Incidência , Adolescente , História do Século XXIRESUMO
The global COVID-19 pandemic illustrates the importance of a close partnership between public health and juvenile justice systems when responding to communicable diseases. Many setting-specific obstacles must be navigated to respond effectively to limit disease transmission and negative health outcomes while maintaining necessary services for youth in confinement facilities. The response requires multidisciplinary expertise and collaboration to address unique considerations. Public health mitigation strategies must balance the risk for disease against the negative effects of restrictions. Key aspects of the COVID-19 response in the juvenile justice system of Colorado, USA, involved establishing robust communication and data reporting infrastructures, building a multidisciplinary response team, adapting existing infection prevention guidelines, and focusing on a whole-person health approach to infection prevention. We examine lessons learned and offer recommendations on pandemic emergency response planning and managing a statewide public health emergency in youth confinement settings that ensure ongoing readiness.
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COVID-19 , Adolescente , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Pandemias/prevenção & controle , Colorado/epidemiologia , Saúde Pública , Análise de SistemasRESUMO
BACKGROUND: Trifluridine/tipiracil (FTD/TPI) plus bevacizumab has shown clinical benefit for metastatic colorectal cancer (mCRC) refractory to standard therapy. However, few data have been available for patients with pretreated mCRC who are intolerant of intensive therapy (vulnerable). METHODS: We performed a multicenter retrospective study (WJOG14520G; TWILIGHT) of FTD/TPI plus bevacizumab for vulnerable patients with pretreated mCRC. Eligibility criteria included previous chemotherapy (although patients treated with all key cytotoxic agents, a fluoropyrimidine, oxaliplatin, and irinotecan, were excluded) and intolerance of full-dose combination therapy with oxaliplatin or irinotecan at the start of FTD/TPI plus bevacizumab. RESULTS: The median age of 93 evaluable patients was 79 years (range, 21-90). Intolerance of intensive therapy was attributable to an older age in 60 (65%) patients, serious concomitant disease in 24 (26%) patients, and a poor performance status in 19 (20%) patients. FTD/TPI plus bevacizumab was administered as second-line treatment in 74 (80%) patients and as third- or fourth-line treatment in 19 (20%) patients. The objective response rate was 4.9% (95% confidence interval [CI], 1.4%-12.2%), and the disease control rate was 67.9% (95% CI, 56.6%-77.8%). With a median follow-up time of 21.6 months, median overall survival and progression-free survival were 18.6 months (95% CI, 12.1-23.2) and 6.3 months (95% CI, 5.0-8.3), respectively. Neutropenia of grade ≥3 developed in 50 (54%) patients, whereas 2 (2%) patients experienced febrile neutropenia, and no treatment-related death was observed. CONCLUSION: Our data show the potential efficacy and acceptable safety profile of FTD/TPI plus bevacizumab for vulnerable patients with pretreated mCRC.
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Neoplasias do Colo , Neoplasias Colorretais , Demência Frontotemporal , Pirrolidinas , Neoplasias Retais , Timina , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Bevacizumab/efeitos adversos , Neoplasias Colorretais/patologia , Estudos Retrospectivos , Uracila , Oxaliplatina/uso terapêutico , Trifluridina/efeitos adversos , Irinotecano/uso terapêutico , Demência Frontotemporal/induzido quimicamente , Demência Frontotemporal/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias do Colo/tratamento farmacológico , Neoplasias Retais/tratamento farmacológico , Combinação de MedicamentosRESUMO
Determining whether an ectopic depolarization will lead to a self-perpetuating arrhythmia is of critical importance in determining arrhythmia risk, so it is necessary to understand what factors impact substrate vulnerability. This study sought to explore the impact of cell-to-cell heterogeneity in ion channel conductance on substrate vulnerability to arrhythmia by measuring the duration of the vulnerable window in computational models of one-dimensional cables of ventricular cardiomyocytes. We began by using a population of uniform cable models to determine the mechanisms underlying the vulnerable window phenomenon. We found that in addition to the known importance of GNa, the conductances GCa,L and GKr also play a minor role in determining the vulnerable window duration. We also found that a steeper slope of the repolarizing action potential during the vulnerable window correlated with a shorter vulnerable window duration in uniform cables. We applied our understanding from these initial simulations to an investigation of the vulnerable window in heterogeneous cable models. The heterogeneous cables displayed a great deal of intra-cable variation in vulnerable window duration, highly sensitive to the cardiomyocytes in the local environment of the ectopic stimulus. Coupling strength modulated not only the magnitude of the vulnerable window duration but also the extent of intra-tissue variability in vulnerable window duration.NEW & NOTEWORTHY We investigate the impact of cell-to-cell heterogeneity in ion channel conductance on substrate vulnerability to arrhythmia by measuring the vulnerable window duration in computational cardiomyocyte cable models. We demonstrate a wide range of intra-cable variability in vulnerable window duration (VWD) and show how this is changed by ion channel block and coupling strength perturbations.
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Potenciais de Ação , Arritmias Cardíacas , Canais Iônicos , Modelos Cardiovasculares , Miócitos Cardíacos , Arritmias Cardíacas/fisiopatologia , Arritmias Cardíacas/metabolismo , Miócitos Cardíacos/metabolismo , Canais Iônicos/metabolismo , Animais , Humanos , Simulação por ComputadorRESUMO
OBJECTIVES: The inJectable Antiretroviral feasiBility Study (JABS) aimed to evaluate the implementation of long-acting regimens in a 'real world' Australian setting, with inclusion of participants with complex medical needs, social vulnerability and/or historical non-adherence. METHODS: JABS was a 12-month, single-centre, single-arm, open-label phase IV study of long-acting cabotegravir 600 mg plus rilpivirine 900 mg administered intramuscularly every 2 months to adults with treated HIV-1 infection. The primary endpoint was the proportion of attendances and administration of injections within a 14-day dosing window over 12 months, out of the total prescribed doses. Secondary endpoints included proportions of missed appointments, use of oral bridging, discontinuations, virological failures, adverse events and participant-reported outcomes. A multidisciplinary adherence programme embedded in the clinical service known as REACH provided support to JABS participants. RESULTS: Of 60 participants enrolled by May 2022, 60% had one or more complexity or vulnerability factors identified, including absence of social supports (50%), mental health issues, alcohol or drug use (30%) and financial hardship or instability (13%), among others. Twenty-seven per cent of participants had historical non-adherence to antiretroviral therapy. Out of 395 prescribed doses, 97.2% of injections were administered within correct dosing windows at clinic visits. Two courses of short-term oral bridging were required. The rate of injection site reactions was 29%, the majority being grade 1-2. There were no virological failures, no serious adverse events and only one injection-related study discontinuation. High baseline treatment satisfaction and acceptability of injections increased by month 12. Those with vulnerability factors had similar adherence to injections as those without such factors. Ninety-eight per cent of the participants who completed 12 months on the study have maintained long-acting therapy, virological suppression and retention in care. CONCLUSIONS: Long-acting cabotegravir plus rilpivirine was associated with very high adherence, maintenance of virological suppression, safety and treatment satisfaction in a diverse Australian clinic population, comparable to results of phase III randomized clinical trials. Individuals with vulnerability factors can achieve adherence to injections with individualized support. Long-acting therapies in this group can increase the subsequent engagement in clinical care.
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Estudos de Viabilidade , Infecções por HIV , Adesão à Medicação , Piridonas , Rilpivirina , Humanos , Rilpivirina/administração & dosagem , Rilpivirina/uso terapêutico , Rilpivirina/efeitos adversos , Masculino , Infecções por HIV/tratamento farmacológico , Feminino , Adulto , Pessoa de Meia-Idade , Injeções Intramusculares , Adesão à Medicação/estatística & dados numéricos , Piridonas/administração & dosagem , Piridonas/efeitos adversos , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/efeitos adversos , Austrália , Resultado do Tratamento , HIV-1/efeitos dos fármacos , DicetopiperazinasRESUMO
OBJECTIVE: To assess the relative risk of mortality in infants born preterm and small for gestational age (SGA) during the first and second months of life in rural Bangladesh. STUDY DESIGN: We analyzed data from a cohort of pregnant women and their babies in Sylhet, Bangladesh, assembled between 2011 and 2014. Community health workers visited enrolled babies up to 10 times from birth to age 59 days. Survival status was recorded at each visit. Gestational age was estimated from mother's reported last menstrual period. Birth weights were measured within 72 hours of delivery. SGA was defined using the INTERGROWTH-21st standard. We estimated unadjusted and adjusted hazard ratios (HRs) and corresponding 95% CIs for babies born preterm and SGA separately for the first and second month of life using bivariate and multivariable weighted Cox regression models. RESULTS: The analysis included 17â643 singleton live birth babies. Compared with infants born at term-appropriate for gestational age, in both unadjusted and adjusted analyses, infants born preterm-SGA had the greatest risk of death in the first (HR 13.25, 95% CI 8.65-20.31; adjusted HR 12.05, 95% CI 7.82-18.57) and second month of life (HR 4.65, 95% CI 1.93-11.23; adjusted HR 4.1, 95% CI 1.66-10.15), followed by infants born preterm-appropriate for gestational age and term-SGA. CONCLUSIONS: The risk of mortality in infants born preterm and/or SGA is increased and extends through the second month of life. Appropriate interventions to prevent and manage complications caused by prematurity and SGA could improve survival during and beyond the neonatal period.
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Mortalidade Infantil , Recém-Nascido Prematuro , Recém-Nascido Pequeno para a Idade Gestacional , População Rural , Humanos , Bangladesh/epidemiologia , Recém-Nascido , Feminino , Estudos Prospectivos , População Rural/estatística & dados numéricos , Masculino , Lactente , Adulto , Gravidez , Idade Gestacional , Nascimento Prematuro/epidemiologia , Adulto Jovem , Estudos de CoortesRESUMO
Hepatitis C virus (HCV) causes significant mortality worldwide. HCV is highly curable but access to care is limited for many patients. The Grady Liver Clinic (GLC), a primary care-based HCV clinic, utilizes a multidisciplinary team to provide comprehensive care for a medically underserved patient population in Atlanta, Georgia. The GLC added a telehealth option for HCV treatment at the start of the COVID-19 pandemic. We describe the outcomes of utilizing telehealth in this population. We performed a retrospective chart review of patients who initiated HCV treatment from March 2019 to February 2020 (pre-pandemic) and March 2020 to February 2021 (pandemic). Charts were abstracted for patient demographics and characteristics, treatment regimen, and treatment outcomes. Our primary outcome was HCV cure rate of the pre-pandemic compared to the pandemic cohorts and within the different pandemic cohort visit types. We performed an intention-to-treat (ITT) analysis for all patients who took at least one dose of a direct-acting antiviral (DAA) regardless of therapy completion, and a per-protocol (PP) analysis of those who completed treatment and were tested for HCV cure. SVR12 rates were >95% on ITT analysis, with no significant difference between pre-pandemic and pandemic cohorts. There was also no significant difference within the pandemic group when treatment was provided traditionally, via telehealth, or via a hybrid of these. Our findings support the use of telehealth as a tool to expand access to HCV treatment in a medically underserved patient population.
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Hepatite C Crônica , Hepatite C , Telemedicina , Humanos , Antivirais/uso terapêutico , Estudos Retrospectivos , Hepatite C Crônica/tratamento farmacológico , Provedores de Redes de Segurança , Pandemias , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , HepacivirusRESUMO
BACKGROUND: The COVID-19 pandemic disproportionately affected people from structurally vulnerable communities. There was a need to improve COVID-19 testing in these communities to reduce viral spread and connect to treatment. OBJECTIVE: We created a partnership between an academic medical center and three community-based organizations (CBOs) to offer low-barrier COVID-19 walk-up testing clinics in Portland, Maine. Our objective was to examine whether the co-created testing clinics reached structurally vulnerable populations. DESIGN: The clinics offered COVID-19 rapid antigen tests three times a week outside CBO sites from January 2022 to May 2023. Clinic staff administered a brief survey on reason for testing and then instructed participants on how to self-swab. While staff processed the test, participants were invited to complete an additional survey about their demographics and testing perceptions. PARTICIPANTS: Adults seeking COVID-19 testing with specific outreach to people who are unhoused, immigrants, and low-income and/or uninsured. MAIN MEASURES: Number of tests conducted and result, reasons for testing, and testing perceptions. KEY RESULTS: Of 246 completed tests, 18 were positive for COVID-19 (7%). Participants sought testing for a variety of reasons, including symptoms (60%), close contact exposure (29%), and/or need for a negative test result to access services or an activity (33%). Overall, people primarily tested due to symptoms with only 7% testing due to close contact exposure alone. The clinics reached vulnerable populations. Among the 130 people completing the participant survey, 39% were unhoused, 22% spoke a language other than English at home, 23% were uninsured, and 46% earned less than $20,000 in 2019. Qualitative field notes captured key elements of clinics that influenced reach, and how this collaboration with CBOs helped build trust with our target populations. CONCLUSIONS: Providing low-barrier walk-up clinics partnering with trusted CBOs was observed to be helpful in reaching structurally vulnerable populations for COVID-19 testing.
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BACKGROUND: The opioid overdose epidemic disproportionately impacts people experiencing homelessness. Outpatient-based opioid treatment (OBOT) programs have been established in homeless health care settings across the USA, but little is known about the success of these programs in engaging and retaining this highly marginalized patient population in addiction care. OBJECTIVE: To evaluate predictors of initial engagement and subsequent attendance in a homeless-tailored OBOT program. DESIGN: Prospective cohort study with 4 months of follow-up. PARTICIPANTS: A total of 148 homeless-experienced adults (≥18 years) who newly enrolled in the Boston Healthcare for the Homeless Program (BHCHP) OBOT program over a 1-year period (1/6/2022-1/5/2023). MAIN MEASURES: The primary outcomes were (1) initial OBOT program engagement, defined as having ≥2 additional OBOT visits within 1 month of OBOT enrollment, and (2) subsequent OBOT program attendance, measured monthly from months 2 to 4 of follow-up. KEY RESULTS: The average age was 41.7 years (SD 10.2); 23.6% were female, 35.8% were Hispanic, 12.8% were non-Hispanic Black, and 43.9% were non-Hispanic White. Over one-half (57.4%) were initially engaged. OBOT program attendances during months 2, 3, and 4 were 60.8%, 50.0%, and 41.2%, respectively. One-quarter (24.3%) were initially engaged and then attended the OBOT program every month during the follow-up period. Participants in housing or residential treatment programs (vs. unhoused; adjusted odds ratios (aORs) = 2.52; 95% CI = 1.17-5.44) and those who were already on or initiated a medication for opioid use disorder (OUD) (aOR = 6.53; 95% CI = 1.62-26.25) at the time of OBOT enrollment had higher odds of engagement. Older age (aOR = 1.74 per 10-year increment; 95% CI = 1.28-2.38) and initial engagement (aOR = 3.50; 95% CI = 1.86-6.59) conferred higher odds of attendance. CONCLUSIONS: In this study, over half initially engaged with the OBOT program, with initial engagement emerging as a strong predictor of subsequent OBOT program attendance. Interventions aimed at enhancing initial OBOT program engagement, including those focused on housing and buprenorphine initiation, may improve longer-term outcomes in this marginalized population.
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BACKGROUND: In older patients, esophageal squamous cell carcinoma (ESCC) is difficult to treat using standard therapies, including surgery and cisplatin-based chemoradiotherapy. Paclitaxel (PTX) has radiosensitizing activity. We conducted a phase I trial of PTX combined with radiotherapy to establish a standard therapy for locally advanced ESCC in older patients. METHODS: Enrollment was conducted at six centers in Japan from April 2016 to September 2019. The participants were aged ≥ 70 years, had locally advanced ESCC, and were intolerant to surgery or unwilling. A fixed 60-Gy radiation dose was administered in 30 fractions. PTX dosing levels started at 30 mg/m2 weekly for 6 weeks. Depending on the number of DLTs, the dose was set to be increased by 10 mg/m2 or switched to biweekly. A geriatric assessment was performed before treatment using the Geriatric-8 screening tool. The primary endpoint was dose-limiting toxicity (DLT). RESULTS: We enrolled 24 patients (6 per group); DLT was observed in one (grade 4 hypokalemia), one (grade 3 aspiration), two (grade 3 radiodermatitis, grade 3 esophageal hemorrhage), and two (grade 3 anorexia, grade 5 pneumonitis) patients in the weekly PTX 30, 40, 50, and 60 mg/m2 groups, respectively. All adverse events, except death in the 60 mg/m2 group, showed reversible improvement, and the safety profile was considered acceptable. The 2-year survival and complete response rates were 40.0% and 54.2%, respectively. There was a significant difference in survival between favorable and unfavorable Geriatric-8 scores. CONCLUSIONS: The recommended PTX dose with concomitant radiation was determined to be 50 mg/m2 weekly. Phase II trials at this dose are underway.
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Quimiorradioterapia , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Paclitaxel , Humanos , Paclitaxel/administração & dosagem , Paclitaxel/uso terapêutico , Idoso , Masculino , Feminino , Quimiorradioterapia/métodos , Carcinoma de Células Escamosas do Esôfago/terapia , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/mortalidade , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/tratamento farmacológico , Idoso de 80 Anos ou mais , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/uso terapêutico , Japão , Resultado do TratamentoRESUMO
Vulnerable populations are a particular group that are not capable of fending for themselves due to a number of limitations. Among many things, of particular concern is the food safety challenges faced by these individuals and the high risk of susceptibility to foodborne diseases. In this paper, an attempt is made to point out the various challenges faced by vulnerable populations that make them more susceptible to foodborne illness than other healthy adults. Also, the paper highlights possible improvement pathways through which these people can have access to safe and nutritious food, and the current interventional steps taken to address the food safety risk associated with food handling activities of food meant for vulnerable groups.
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Manipulação de Alimentos , Inocuidade dos Alimentos , Doenças Transmitidas por Alimentos , Populações Vulneráveis , Humanos , Doenças Transmitidas por Alimentos/prevenção & controle , Adulto , Abastecimento de Alimentos , Manipulação de Alimentos/métodos , Manipulação de Alimentos/normasRESUMO
Inflammation induced by activated macrophages within vulnerable atherosclerotic plaques (VAPs) constitutes a significant risk factor for plaque rupture. Translocator protein (TSPO) is highly expressed in activated macrophages. This study investigated the effectiveness of TSPO radiotracers, 18F-FDPA, in detecting VAPs and quantifying plaque inflammation in rabbits. 18 New Zealand rabbits were divided into 3 groups: sham group A, VAP model group B, and evolocumab treatment group C. 18F-FDPA PET/CTA imaging was performed at 12, 16, and 24 weeks in all groups. Optical coherence tomography (OCT) was performed on the abdominal aorta at 24 weeks. The VAP was defined through OCT images, and ex vivo aorta PET imaging was also performed at 24 weeks. The SUVmax and SUVmean of 18F-FDPA were measured on the target organ, and the target-to-background ratio (TBRmax) was calculated as SUVmax/SUVblood pool. The arterial sections of the isolated abdominal aorta were analyzed by HE staining, CD68 and TSPO immunofluorescence staining, and TSPO Western blot. The results showed that at 24 weeks, the plaque TBRmax of 18F-FDPA in group B was significantly higher than in groups A and C. Immunofluorescence staining of CD68 and TSPO, as well as Western blot, confirmed the increased expression of macrophages and TSPO in the corresponding regions of group B. HE staining revealed an increased presence of the lipid core, multiple foam cells, and inflammatory cell infiltration in the area with high 18F-FDPA uptake. This indicates a correlation between 18F-FDPA uptake, inflammation severity, and VAPs. The TSPO-targeted tracer 18F-FDPA shows specific uptake in macrophage-rich regions of atherosclerotic plaques, making it a valuable tool for assessing inflammation in VAPs.
Assuntos
Inflamação , Placa Aterosclerótica , Tomografia por Emissão de Pósitrons , Animais , Coelhos , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/metabolismo , Inflamação/metabolismo , Inflamação/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Masculino , Macrófagos/metabolismo , Receptores de GABA/metabolismo , Compostos Radiofarmacêuticos/farmacocinética , Aorta Abdominal/diagnóstico por imagem , Aorta Abdominal/metabolismo , Aorta Abdominal/patologia , Radioisótopos de Flúor , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , AcetanilidasRESUMO
It is well established that individuals differ in their response to sleep loss. However, existing methods to predict an individual's sleep-loss phenotype are not scalable or involve effort-dependent neurobehavioural tests. To overcome these limitations, we sought to predict an individual's level of resilience or vulnerability to sleep loss using electroencephalographic (EEG) features obtained from routine night sleep. To this end, we retrospectively analysed five studies in which 96 healthy young adults (41 women) completed a laboratory baseline-sleep phase followed by a sleep-loss challenge. After classifying subjects into sleep-loss phenotypic groups, we extracted two EEG features from the first sleep cycle (median duration: 1.6 h), slow-wave activity (SWA) power and SWA rise rate, from four channels during the baseline nights. Using these data, we developed two sets of logistic regression classifiers (resilient versus not-resilient and vulnerable versus not-vulnerable) to predict the probability of sleep-loss resilience or vulnerability, respectively, and evaluated model performance using test datasets not used in model development. Consistently, the most predictive features came from the left cerebral hemisphere. For the resilient versus not-resilient classifiers, we obtained an average testing performance of 0.68 for the area under the receiver operating characteristic curve, 0.72 for accuracy, 0.50 for sensitivity, 0.84 for specificity, 0.61 for positive predictive value, and 3.59 for likelihood ratio. We obtained similar performance for the vulnerable versus not-vulnerable classifiers. These results indicate that logistic regression classifiers based on SWA power and SWA rise rate from routine night sleep can largely predict an individual's sleep-loss phenotype.
RESUMO
PURPOSE: To understand racial disparities in germline cancer genetic testing and the role of prior knowledge, attitudes, and sources of information. METHODS: A cross-sectional analysis of the Health Information National Trends Survey 5 (HINTS 5) was conducted between February 24th and June 15th, 2020. The study aimed to investigate knowledge and receipt of genetic testing, attitudes toward the importance of genetic testing in preventing, detecting, and treating cancer, and information sources of genetic testing in the United States of America. RESULTS: Non-Hispanic Black (NHB) and Hispanic race/ethnicity were associated with lower odds of being informed about genetic testing, whereas those of NHB race were more likely to endorse the importance of genetic testing in cancer prevention and treatment. Regarding sources of information about genetic testing: Non-Hispanic Asians were less likely to be informed about genetic testing from television (Mean Predicted Probability (MPP) 0.38 95%CI; 0.21-0.55, (Adjusted Risk Difference) ARD vs. Non-Hispanic White (NHW); -0.228, p = 0.01), NHB were less likely to report being informed about genetic testing from social media (MPP 0.27 95%CI; 0.20-0.34, ARD vs. NHW; -0.139, p < 0.01). CONCLUSIONS: NHB and Hispanic groups face unequal access to information about genetic testing. There are significant race-based differences in information sources. These differences could be used to promote equitable access to cancer genetic testing.
Assuntos
Acesso à Informação , Testes Genéticos , Conhecimentos, Atitudes e Prática em Saúde , Disparidades em Assistência à Saúde , Neoplasias , Humanos , Negro ou Afro-Americano , Estudos Transversais , Células Germinativas , Neoplasias/diagnóstico , Neoplasias/genética , Fatores Raciais , Estados Unidos , Hispânico ou LatinoRESUMO
Sexual and gender minority (SGM) adults experience poor health outcomes, in part due to frequent avoidance of necessary health care. Little is known, however, about factors contributing to patterns of health care utilization in this population. Using national data from the All of Us Research Program, this study evaluated the prevalence of care avoidance due to patient-clinician identity discordance (PCID) and its association with health care discrimination among SGM adults. Sexual minority (20.0% vs 9.4%; adjusted rate ratio [aRR] = 1.58; 95% CI, 1.49-1.67, P <0.001) and gender minority adults (34.4% vs 10.3%; aRR = 2.00; 95% CI, 1.79-2.21, P <0.001) were significantly more likely than their non-SGM counterparts to report care avoidance due to PCID. Exposure to health care discrimination was also more prevalent in this population and was dose-dependently associated with significantly higher rates of PCID-based care avoidance. Study findings highlight the importance of diversifying the health care workforce, expanding SGM-related clinical training, and preventing health care discrimination against SGM patients.
Assuntos
Minorias Sexuais e de Gênero , Humanos , Minorias Sexuais e de Gênero/estatística & dados numéricos , Minorias Sexuais e de Gênero/psicologia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Estados Unidos , Relações Médico-Paciente , Adulto Jovem , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Adolescente , IdosoRESUMO
We are beginning to accept and address the role that medicine as an institution played in legitimizing scientific racism and creating structural barriers to health equity. There is a call for greater emphasis in medical education on explaining our role in perpetuating health inequities and educating learners on how bias and racism lead to poor health outcomes for historically marginalized communities. Diversity, equity, and inclusion (DEI; also referred to as EDI) and antiracism are key parts of patient care and medical education as they empower health professionals to be advocates for their patients, leading to better health care outcomes and more culturally and socially humble health care professionals. The Liaison Committee on Medical Education has set forth standards to include structural competency and other equity principles in the medical curriculum, but medical schools are still struggling with how to specifically do so. Here, we highlight a stepwise approach to systematically developing and implementing medical educational curriculum content with a DEI and antiracism lens. This article serves as a blueprint to prepare institution leadership, medical faculty, staff, and learners in how to effectively begin or scale up their current DEI and antiracism curricular efforts.