The influence of socioeconomic status on individual attitudes and experience with clinical trials.

BACKGROUND: Characterizing perceptions of clinical trials among the socioeconomically disadvantaged is necessary for understanding how social determinants of health such as socioeconomic disparities in education and income can affect people's awareness of and exposure to clinical trials METHODS: A survey was distributed in spring 2023 among a survey taking sample stratified by demographic variables to reflect the U.S. POPULATION: The survey assessed the socioeconomic status of the respondent and related covariates, as well as outcome measures including interest in joining a clinical trial, concerns relating to participation, and whether the respondent had previously been asked to participate. Multiple and logistic regression were used to assess the relationship between predictor and outcome variables RESULTS: Here we show the results of outcome measures regressed on main predictors related to socioeconomic status and related demographic predictors. Education, employment status, insurance coverage, and English proficiency were significant predictors of interest in clinical trial participation. Education and the presence of a healthcare professional or former clinical trial participant in the respondent's personal network were significant predictors of whether the respondent had previously been asked to participate in a clinical trial CONCLUSIONS: The results of the analysis reveal how socioeconomically vulnerable groups, including those from low income and low education groups, are being excluded in clinical research. Analyses also uncovered the impact of clinical trial social influence-the presence of having a family or friend in one's social network who participated in a clinical trial-on willingness to participate and exposure to clinical trials.

Participation in clinical trials has remained largely inaccessible to historically underrepresented communities, which includes groups that are low income and low education. Here, we examine socioeconomic and demographic factors that can influence individuals' willingness to participate in clinical trials and their experience being asked to participate in clinical trials. Using several types of analysis, we show that those who are low income and less educated are less willing to participate in clinical trials and are less likely to be asked to participate in clinical trials when compared to those with higher income and more education. This highlights the need for improved outreach among healthcare providers and clinical research staff to include these communities and provide individuals with the knowledge, awareness, and opportunity to participate in clinical trials.

Phase 1 dose-escalation trial evaluating a group 2 influenza hemagglutinin stabilized stem nanoparticle vaccine.

The relative conservation of the influenza hemagglutinin (HA) stem compared to that of the immunodominant HA head makes the HA stem an attractive target for broadly protective influenza vaccines. Here we report the first-in-human, dose-escalation, open-label trial (NCT04579250) evaluating an unadjuvanted group 2 stabilized stem ferritin nanoparticle vaccine based on the H10 A/Jiangxi-Donghu/346/2013 influenza HA, H10ssF, in healthy adults. Participants received a single 20 mcg dose (n = 3) or two 60 mcg doses 16 weeks apart (n = 22). Vaccination with H10ssF was safe and well tolerated with only mild systemic and local reactogenicity reported. No serious adverse events occurred. Vaccination significantly increased homologous H10 HA stem binding and neutralizing antibodies at 2 weeks after both first and second vaccinations, and these responses remained above baseline at 40 weeks. Heterologous H3 and H7 binding antibodies also significantly increased after each vaccination and remained elevated throughout the study. These data indicate that the group 2 HA stem nanoparticle vaccine is safe and induces stem-directed binding and neutralizing antibodies.

Mapping Strategies for Reaching Socioeconomically Disadvantaged Populations in Clinical Trials.

Importance: Socioeconomically disadvantaged patients, such as persons with low income and those with low educational attainment, are less likely to participate in clinical trials than those with higher earnings and higher educational attainment, despite the former being more likely to have chronic medical conditions. Ways to improve the representation of socioeconomically disadvantaged patients in clinical trials deserve attention. Objective: To examine whether current recruitment and enrollment strategies used by US clinical research sites appropriately include patients from socioeconomically disadvantaged backgrounds. Design, Setting, and Participants: This survey study was conducted between April and July 2023. An online survey was distributed among US clinical research sites to explore their use of these strategies and the types of patient sociodemographic and socioeconomic data they collect. The survey was distributed by 13 pharmaceutical companies and 1 clinical research organization. Eight targeted strategies known to increase the recruitment and retention of socioeconomically disadvantaged participants as well as 6 general strategies to recruit and retain clinical trial participants were identified. Data analysis was performed between August and September 2023. Main Outcomes and Measures: Proportions of for-profit vs nonprofit or governmental sites that use recruitment and retention strategies, proportions that have partnerships with community organizations that target socioeconomically disadvantaged groups, and the distribution of sociodemographic and socioeconomic data collected by sites about their patients. A χ2 test of independence was performed to assess the association between research site ownership type and levels of adoption of strategies. Results: A total of 492 responses were collected from 381 clinical research sites in the US (219 for-profit sites [57.5%] and 162 nonprofit or governmental sites [42.5%]). Overall, compared with nonprofit or governmental sites, for-profit sites reported higher use of strategies shown to increase the recruitment and retention of socioeconomically disadvantaged populations, including always or often providing after-hours visits (84 of 173 for-profit sites [48.6%]; 22 of 123 nonprofit or governmental sites [17.9%]) and offering financial compensation (135 of 162 for-profit sites [83.3%]; 60 of 123 nonprofit or governmental sites [48.8%]). Additionally, there was an association between research site ownership type and levels of adoption of these strategies; for example, for-profit sites were more likely to provide after-hours visits (χ2 = 30.33; P < .001) and offer financial compensation (χ2 = 49.35; P < .001). Only 7.2% of for-profit sites (12 of 167) and 13.0% of nonprofit or governmental sites (16 of 123) collected information on the patient's annual income. Conclusions and Relevance: In this survey study, we found an association between a clinical research site's ownership type (for-profit vs nonprofit or governmental) and how often it used strategies to engage socioeconomically diverse populations in clinical research. Regardless of ownership type, most clinical research sites did not collect socioeconomic information from patients. Adoption of strategies to engage socioeconomically diverse populations, particularly by nonprofit or governmental sites, may help minimize barriers to participation for socioeconomically disadvantaged patients.

Comprehensive Assessment of Risk-Based Quality Management Adoption in Clinical Trials.

BACKGROUND: Risk-based monitoring (RBM) and risk-based quality management (RBQM) offer a compelling approach to increase efficiency, speed and quality in clinical trials by prioritizing and mitigating risks related to essential safety and efficacy data. Since 2013, the FDA and EMA have encouraged the use of RBM/RBQM, however adoption has been slow with limited understanding of the barriers to adoption. METHODS: The Tufts Center for the Study of Drug Development conducted an online survey among pharmaceutical, biotechnology, and contract research organizations and gathered 206 responses on 32 distinct RBQM practices. RESULTS: On average, companies implemented RBQM in 57% of their clinical trials. Lower levels of adoption were observed among companies conducting fewer than 25 trials annually (48%) compared to those conducting more than 100 trials annually (63%). Primary barriers to adoption include lack of organizational knowledge and awareness, mixed perceptions of the value proposition of RBQM, and poor change management planning and execution. Insights into improving the level of adoption are discussed.

Quantifying Site Burden to Optimize Protocol Performance.

BACKGROUND: The increase in protocol complexity and the resulting rise in the effort required by investigative sites to implement protocols have been well documented, but existing measures of site burden only offer an incomplete view of the burden experienced by site personnel. The introduction of Decentralized Clinical Trials-trials supported by remote and virtual technologies and services-is expected to impact the burden imposed on sites, but this impact has not yet been systematically measured. METHODS: The Tufts Center for the Study of Drug Development conducted an online survey among clinical research sites worldwide and gathered 355 responses assessing the burden associated with distinct activities and procedures related to the implementation of clinical trial protocols using traditional and decentralized approaches. RESULTS: A high percentage of investigative sites (50.5%) have had no experience with DCT solutions and only a small percentage (6.6%) have participated in fully decentralized clinical trials. Overall, half of respondents view DCT solutions as more burdensome than traditional clinical trials. In general, activities related to operational and managerial aspects of trial implementation were viewed as less burdensome when done remotely, while clinical procedures or elements that require study team-patient interactions were viewed as more burdensome when using DCT approaches versus in-person or traditional methods.

Deconstructing Cultural Aspects of Mental Health Care in Hispanic/Latinx People.

In the United States, 18.9% of the population identifies as Hispanic or Latin. The culture of these communities is as diverse, heterogenous, and rich as the history of this population. Culture shapes the perception of symptoms and psychiatric disorders. To provide culturally sensitive care, it is relevant to understand the history of these communities in the US, recognize cultural humility, and acknowledge aspects and values (eg, culturally bound syndromes, familism, paternalism, stigma of mental illness, machismo, immigration) inherent to the cultural experience and unique barriers to care. Incorporating these aspects into clinical practice is essential for positive outcomes. The purpose of this article is to give a brief historical context, encourage cultural humility, and describe cultural aspects that are essential when providing culturally sensitive care to the Hispanic and Latinx community in the US.

Characterization of active films of chitosan containing nettle Urtica dioica L. extract: Spectral and water properties, microstructure, and antioxidant activity.

Chitosan films enriched with aqueous nettle extract (Urtica dioica L.) were evaluated by measuring their solubility, equilibrium moisture, water vapor permeability, spectral and antioxidant properties, and microstructure. Nettle extract showed a significant effect on the analyzed film properties. The addition of nettle extract manifested a sharp decrease in water vapor permeability, decreasing from 5.64 · 10-11 to 2.22 · 10-11 g/m·s·Pa. The chitosan- nettle extract films exhibited a high free-radical scavenging activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS). Incorporation of nettle extract into the chitosan matrix was successfully carried out to obtain antioxidant films. The results obtained showed that the incorporation of nettle extract allowed obtaining chitosan films with antioxidant properties, including a total phenolic content up to 1.57 mg GAE/g film. Furthermore, the films with nettle extract boast an UV shielding ability with transmittance values close to zero in the UV region and a water solubility up to 1 %. The inherent biodegradability is also a strong advantage of the developed active films.

Genetic Characterization of Extensively Drug-Resistant Shigella sonnei Infections, Spain, 2021-2022.

In 2022, the United Kingdom reported an increase in drug resistance in Shigella sonnei isolates. We report 33 cases in Spain genetically related to the UK cases and 4 cases with similar antimicrobial resistance profiles infected with genetically distant strains. Our results suggest circulation of multiple genetic clusters of multidrug-resistant S. sonnei in Spain.

Vaccine elicitation and structural basis for antibody protection against alphaviruses.

Alphaviruses are RNA viruses that represent emerging public health threats. To identify protective antibodies, we immunized macaques with a mixture of western, eastern, and Venezuelan equine encephalitis virus-like particles (VLPs), a regimen that protects against aerosol challenge with all three viruses. Single- and triple-virus-specific antibodies were isolated, and we identified 21 unique binding groups. Cryo-EM structures revealed that broad VLP binding inversely correlated with sequence and conformational variability. One triple-specific antibody, SKT05, bound proximal to the fusion peptide and neutralized all three Env-pseudotyped encephalitic alphaviruses by using different symmetry elements for recognition across VLPs. Neutralization in other assays (e.g., chimeric Sindbis virus) yielded variable results. SKT05 bound backbone atoms of sequence-diverse residues, enabling broad recognition despite sequence variability; accordingly, SKT05 protected mice against Venezuelan equine encephalitis virus, chikungunya virus, and Ross River virus challenges. Thus, a single vaccine-elicited antibody can protect in vivo against a broad range of alphaviruses.

An influenza hemagglutinin stem nanoparticle vaccine induces cross-group 1 neutralizing antibodies in healthy adults.

Influenza vaccines could be improved by platforms inducing cross-reactive immunity. Immunodominance of the influenza hemagglutinin (HA) head in currently licensed vaccines impedes induction of cross-reactive neutralizing stem-directed antibodies. A vaccine without the variable HA head domain has the potential to focus the immune response on the conserved HA stem. This first-in-human dose-escalation open-label phase 1 clinical trial (NCT03814720) tested an HA stabilized stem ferritin nanoparticle vaccine (H1ssF) based on the H1 HA stem of A/New Caledonia/20/1999. Fifty-two healthy adults aged 18 to 70 years old enrolled to receive either 20 µg of H1ssF once (n = 5) or 60 µg of H1ssF twice (n = 47) with a prime-boost interval of 16 weeks. Thirty-five (74%) 60-µg dose participants received the boost, whereas 11 (23%) boost vaccinations were missed because of public health restrictions in the early stages of the COVID-19 pandemic. The primary objective of this trial was to evaluate the safety and tolerability of H1ssF, and the secondary objective was to evaluate antibody responses after vaccination. H1ssF was safe and well tolerated, with mild solicited local and systemic reactogenicity. The most common symptoms included pain or tenderness at the injection site (n = 10, 19%), headache (n = 10, 19%), and malaise (n = 6, 12%). We found that H1ssF elicited cross-reactive neutralizing antibodies against the conserved HA stem of group 1 influenza viruses, despite previous H1 subtype head-specific immunity. These responses were durable, with neutralizing antibodies observed more than 1 year after vaccination. Our results support this platform as a step forward in the development of a universal influenza vaccine.

Hands-On Ultrasound Training for Radiology Residents: The Impact of an Ultrasound Scanning Curriculum.

RATIONALE AND OBJECTIVES: Radiologists are responsible for interpreting ultrasound (US) images accurately, troubleshooting, aiding sonographers, and advancing technology and research. Despite this, most radiology residents do not feel confident performing US independently. The purpose of this study is to evaluate the impact of an abdominal US scanning rotation and digital curriculum on radiology residents' confidence and skills in performing US. MATERIALS AND METHODS: All residents who were rotating in pediatric US at our institution for the first time were included (PGY 3-5). Those who agreed to participate were recruited sequentially from July 2018 to 2021 into (A) control and (B) intervention. B had a 1-week US scanning rotation and US digital course. Both groups completed a pre-and post-confidence self-assessment. Pre-and post-skills were objectively assessed by an expert technologist while participants scanned a volunteer. At completion, B completed an evaluation of the tutorial. Descriptive statistics summarized the demographics and closed questions. Pre-and post-test results were compared using paired-T tests, and effect size (ES) with Cohen's d. Open-ended questions were thematically analyzed. RESULTS: PGY-3 and 4 residents participated, and were enrolled in A (N = 39) and B (N = 30). Scanning confidence significantly improved in both groups, with a greater ES in B (p < 0.01). Scanning skills significantly improved in B (p < 0.01) but not A. Eighty per cent of questionnaire responders used the integrative US tutorial and found it helpful. Free text responses were grouped into themes: 1) Technical issues, 2) Didn't complete course, 3) Didn't understand project, 4) Course was detailed and thorough. CONCLUSIONS: Our scanning curriculum improved residents' confidence and skills in pediatric US and may encourage consistency in training, thus promoting stewardship of high-quality US.

Clinical perspective in relation to age in patients treated with thrombectomy for anterior circulation stroke in a stroke center in Colombia.

BACKGROUND AND AIMS: Endovascular treatment for cerebrovascular disease is accepted as a first-line option with level I evidence in patients with an early and late time of window of onset symptoms, and an additional option in patients who do not respond or with contraindications to systemic thrombolysis; nevertheless the efficacy and outcomes of some groups were not clear, one of them are patients aged 80 years and older, because they were excluded of the trials, so the evidence is controversial with significant heterogeneity, for that reason in our study, we decided to analyze the age in the patients treated in our stroke center, as a predictor of prognosis, and to provide a baseline for the establishment of personalized treatment plans. METHODS: Observational, retrospective study of patients that received endovascular treatment for cerebrovascular disease in a Colombian stroke center between 2016 and 2020, continuous and categorical variables were compared using the Student's t test and Chi-Square. To determine cut-off points in the variable against death and Rankin score variable on 90th day. RESULTS: In total, 108 patients were recruited, 35 of them were of 80 or more years, and the mean age was 72.7 years, we found age as a significant variable to predict the risk in the population over 80 years of age [RR 3.37 CI (95% 1.14-103) p = 0.029]. CONCLUSIONS: Age younger than 80 is a significant predictor for results and long-term outcomes in patients suffering from stroke, and in patients older than 80 years old a Thrombolysis in Cerebral Infarction score 2b-3 is a predictor of good outcomes. Further studies are needed to evaluate the relationship between intrahospital complications and long-term outcomes.

Selected Biopolymers' Processing and Their Applications: A Review.

Petroleum-based polymers are used in a multitude of products in the commercial world, but their high degree of contamination and non-biodegradability make them unattractive. The development and use of polymers derived from nature offer a solution to achieve an environmentally friendly and green alternative and reduce waste derived from plastics. This review focuses on showing an overview of the most widespread production methods for the main biopolymers. The parameters affecting the development of the technique, the most suitable biopolymers, and the main applications are included. The most studied biopolymers are those derived from polysaccharides and proteins. These biopolymers are subjected to production methods that improve their properties and modify their chemical structure. Process factors such as temperature, humidity, solvents used, or processing time must be considered. Among the most studied production techniques are solvent casting, coating, electrospinning, 3D printing, compression molding, and graft copolymerization. After undergoing these production techniques, biopolymers are applied in many fields such as biomedicine, pharmaceuticals, food packaging, scaffold engineering, and others.

Evaluación de ingesta dietética según el nivel socioeconómico en un grupo de personas vegetarianas en Colombia

Diferentes estudios han relacionado el nivel socioeconómico con la calidad de la dieta y la prevalencia de riesgo de deficiencia de nutrientes. En personas vegetarianas, cuando no se sigue una dieta adecuada, existe la posibilidad de tener una baja ingesta de ciertos nutrientes, principalmente de vitamina B12, vitamina D, calcio, hierro, zinc, ácidos grasos omega-3 y proteínas. Este estudio tiene como objetivo evaluar la ingesta dietética en personas vegetarianas según su nivel socioeconómico en una región de Colombia. Los participantes completaron un cuestionario en el cual se les preguntó por variables socioeconómicas, antropométricas y la frecuencia de consumo de 48 alimentos y suplementos. Posteriormente, a un subgrupo de la muestra se le realizaron dos recordatorios de 24 horas en diferentes días de la semana. Se encontró que, a menor nivel socioeconómico, hay un menor consumo de lácteos, cereales integrales, frutas y verduras. Así mismo, se observó que según el tipo de vegetarianismo hay diferencias en el consumo de cobalamina, fibra y calcio. Se concluye que, de manera similar a los omnívoros, se requiere de educación nutricional para mejorar la elección de los alimentos y lograr suplir los requerimientos nutricionales, independientemente del nivel económico.

Different studies have related socioeconomic status to diet quality and the prevalence of nutrient deficiency risk. Among vegetarians, when an adequate diet is not followed, there is a possibility of having a low intake of certain nutrients, mainly vitamin B12, vitamin D, calcium, iron, zinc, omega-3 fatty acids and proteins. This study aims to evaluate the dietary intake of vegetarians according to their socioeconomic level in a region of Colombia. Participants completed a questionnaire in which they were asked about socioeconomic and anthropometric variables and the frequency of consumption of 48 foods and supplements. Subsequently, a subgroup of the sample was given two 24-hour reminders on different days of the week. We found that the lower the socioeconomic level, the lower the consumption of dairy products, whole grains, fruits and vegetables. Likewise, it was observed that depending on the type of vegetarianism, there are differences in the consumption of cobalamin, fiber and calcium. We conclude that, similar to omnivores, nutritional education is required to improve the choice of foods and to meet nutritional requirements, regardless of economic level.

Artificial Intelligence Curriculum Needs Assessment for a Pediatric Radiology Fellowship Program: What, How, and Why?

RATIONALE AND OBJECTIVES: Artificial intelligence (AI) holds enormous potential for improvements in patient care, efficiency, and innovation in pediatric radiology practice. Although there is a pressing need for a radiology-specific training curriculum and formalized AI teaching, few resources are available. The purpose of our study was to perform a needs assessment for the development of an AI curriculum during pediatric radiology training and continuing education. MATERIALS AND METHODS: A focus group study using a semistructured moderator-guided interview was conducted with radiology trainees' and attending radiologists' perceptions of AI, perceived competence in interpretation of AI literature, and perceived expectations from radiology AI educational programs. The focus group was audio-recorded, transcribed, and thematic analysis was performed. RESULTS: The focus group was held virtually with seven participants. The following themes we identified: (1) AI knowledge, (2) previous training, (3) learning preferences, (4) AI expectations, and (5) AI concerns. The participants had no previous formal training in AI and variability in perceived needs and interests. Most preferred a case-based approach to teaching AI. They expressed incomplete understanding of AI hindered its clinical applicability and reiterated a need for improved training in the interpretation and application of AI literature in their practice. CONCLUSION: We found heterogeneity in perspectives about AI; thus, a curriculum must account for the wide range of these interests and needs. Teaching the interpretation of AI research methods, literature critique, and quality control through implementation of specific scenarios could engage a variety of trainees from different backgrounds and interest levels while ensuring a baseline level of competency in AI.

Heterologous Expression and Immunogenic Potential of the Most Abundant Phospholipase A2 from Coral Snake Micrurus dumerilii to Develop Antivenoms.

Micrurus dumerilii is a coral snake of clinic interest in Colombia. Its venom is mainly composed of phospholipases A2 being MdumPLA2 the most abundant protein. Nevertheless, Micrurus species produce a low quantity of venom, which makes it difficult to produce anticoral antivenoms. Therefore, in this work, we present the recombinant expression of MdumPLA2 to evaluate its biological activities and its immunogenic potential to produce antivenoms. For this, a genetic construct rMdumPLA2 was cloned into the pET28a vector and expressed heterologously in bacteria. His-rMdumPLA2 was extracted from inclusion bodies, refolded in vitro, and isolated using affinity and RP-HPLC chromatography. His-rMdumPLA2 was shown to have phospholipase A2 activity, a weak anticoagulant effect, and induced myonecrosis and edema. The anti-His-rMdumPLA2 antibodies produced in rabbits recognized native PLA2, the complete venom of M. dumerilii, and a phospholipase from another species of the Micrurus genus. Antibodies neutralized 100% of the in vitro phospholipase activity of the recombinant toxin and a moderate percentage of the myotoxic activity of M. dumerilii venom in mice. These results indicate that His-rMdumPLA2 could be used as an immunogen to improve anticoral antivenoms development. This work is the first report of an M. dumerilii functional recombinant PLA2.

Antioxidant Extracts of Nettle (Urtica dioica) Leaves: Evaluation of Extraction Techniques and Solvents.

Nettle (Urtica dioica) is a great source of bioactive compounds. The objective of this study was to evaluate the extraction techniques (ultrasound, without stirring, and stirring), solvents (methanol, water, and ethanol), and extraction times (1-4 h) to maximize antioxidant capacity of the Urtica dioica extracts. In the case of total phenolic content (TPC) and ABTS•+ (2,2-azino-bis(3-etilbenzotiazolin)-6-sulfonic acid) free radical scavenging values, ultrasound extraction was the most efficient method, while the best results of DPPH• (1,1-diphenyl-2-picrylhydrazyl) assay in nettle extracts (91.08%) were obtained using stirring extraction, water as solvent, and 3 h of extraction time. Based on the obtained mathematical models, the optimization revealed that the best extraction conditions were ultrasound treatment with water as solvent and an extraction time of 3.15 h, obtaining values of 21.9 mg eq gallic acid/g dried nettle for TPC, 71.8% for %ABTS•+ and 86.6% for %DPPH•. This work proves that aqueous extract of nettle leaves through the ultrasound technique is an important source of natural antioxidants and can be considered a potential alternative to synthetic antioxidants.

Global Investigative Site Personnel Diversity and Its Relationship with Study Participant Diversity.

BACKGROUND: There is little to no empirical data on the race and ethnicity of the global community of professionals conducting clinical trials funded by pharmaceutical and biotechnology companies and little empirical evidence on the relationship between the race and ethnicity of investigative site personnel and the overall and corresponding diversity of participants enrolled. METHODS: A global online survey conducted in mid-2021 gathered responses from 3462 clinical research professionals representing approximately 3300 distinct investigative sites. RESULTS: Worldwide, including all research settings, the majority (64%) of investigative site personnel are White, 20% are LatinX, 6% are Black, 7% are Asian and 3% are other races and ethnicities (e.g., indigenous peoples, Pacific Islander, Middle Eastern, etc.). The representation of non-white site personnel is significantly higher in North America and Rest of World (ROW) compared to Europe. The highest levels of personnel diversity are found in private community-based practices, investigative sites and site networks. A significant correlation (p < 0.001) was found between site personnel diversity and patient enrollment diversity worldwide. As the mix of site personnel by race and ethnicity increases, the diversity of patients enrolled-except for Asian patients in sites outside of North America-also increases. A significant relationship was also found between the proportion of a given race or ethnicity of investigative site personnel and the corresponding race and ethnicity of patients enrolled. CONCLUSIONS: An opportunity exists to address under-representation in clinical trials through identifying, hiring and supporting investigative site personnel to best reflect the patient communities that they serve.